Endocytosis is characterized by vesicular transport along numerous pathways. Common steps in each pathway include membrane budding to form vesicles, transport to a particular destination, and ultimately docking and fusion with the target membrane. Specificity of vesicle targeting is rendered in part by associated Rab GTPases. This review summarizes current knowledge about Rab GTPase functions in the endocytic pathways and provides insight into the regulation of Rab GTPase activity and mechanisms of Rab protein function. Functional assays have identified some Rab proteins that operate on individual pathways, but Rab proteins in several pathways remain controversial or have not been identified. Control of Rab GTPase activity is exerted through multiple levels of regulation. Significant new information pertaining to Rab protein function in regulating transport has emerged. Remarkably, Rab5 GTPase links budding, cytoskeletal transport and docking/fusion activities. This paradigm will most likely be generally applicable to other Rab GTPase pathways. Together with the cross-talk between different Rab proteins and their effectors, this may provide an integrated system for the general coordination of endocytic pathways to maintain organelle homeostasis.

REFERENCES

Alexandrov
K.
,
Horiuchi
H.
,
Steele-Mortimer
O.
,
Seabra
M. C.
,
Zerial
M.
(
1994
).
Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes.
EMBO J
13
,
5262
5273
Alvarez-Dominguez
C.
,
Stahl
P. D.
(
1998
).
Interferon-gamma selectively induces Rab5a synthesis and processing in mononuclear cells.
J. Biol. Chem
273
,
33901
33904
Apodaca
G.
,
Katz
L. A.
,
Mostov
K. E.
(
1994
).
Receptor-mediated transcytosis of IgA in MDCK cells is via apical recycling endosomes.
J. Cell Biol
125
,
67
86
Ayad
N.
,
Hull
M.
,
Mellman
I.
(
1997
).
Mitotic phosphorylation of rab4 prevents binding to a specific receptor on endosome membranes.
EMBO J
16
,
4497
4507
Bailly
E.
,
McCaffrey
M.
,
Touchot
N.
,
Zahraoui
A.
,
Goud
B.
,
Bornens
M.
(
1991
).
Phosphorylation of two small GTP-binding proteins of the Rab family by p34cdc2.
Nature
350
,
715
718
Barbieri
M. A.
,
Roberts
R. L.
,
Mukhopadhyay
A.
,
Stahl
P. D.
(
1996
).
Rab5 regulates the dynamics of early endosome fusion.
Biocell
20
,
331
338
Barbieri
M. A.
,
Kohn
A. D.
,
Roth
R. A.
,
Stahl
P. D.
(
1998
).
Protein kinase B/akt and Rab5 mediate Ras activation of endocytosis.
J. Biol. Chem
273
,
19367
19370
Barroso
M.
,
Nelson
D. S.
,
Sztul
E.
(
1995
).
Transcytosis-associated protein (TAP)/p115 is a general fusion factor required for binding of vesicles to acceptor membranes.
Proc. Nat. Acad. Sci. USA
92
,
527
531
Bean
A. J.
,
Seifert
R.
,
Chen
Y. A.
,
Sacks
R.
,
Scheller
R. H.
(
1997
).
Hrs-2 is an ATPase implicated in calcium-regulated secretion.
Nature
385
,
826
829
Bright
N. A.
,
Reaves
B. J.
,
Mullock
B. M.
,
Luzio
J. P.
(
1997
).
Dense core lysosomes can fuse with late endosomes and are re-formed from the resultant hybrid organelles.
J. Cell Sci
110
,
2027
2040
Brown
W. J.
,
DeWald
D. B.
,
Emr
S. D.
,
Plutner
H.
,
Balch
W. E.
(
1995
).
Role for phosphatidylinositol 3-kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells.
J. Cell Biol
130
,
781
796
Bucci
C.
,
Parton
R. G.
,
Mather
I. H.
,
Stunnenberg
H.
,
Simons
K.
,
Hoflack
B.
,
Zerial
M.
(
1992
).
The small GTPase Rab5 functions as a regulatory factor in the early endocytic pathway.
Cell
70
,
715
728
Bucci
C.
,
Wandinger-Ness
A.
,
Lutcke
A.
,
Chiariello
M.
,
Bruni
C. B.
,
Zerial
M.
(
1994
).
Rab5a is a common component of the apical and basolateral endocytic machinery in polarized epithelial cells.
Proc. Nat. Acad. Sci. USA
91
,
5061
5065
Burd
C. G.
,
Emr
S. D.
(
1998
).
Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains.
Mol. Cell
2
,
157
162
Calhoun
B. C.
,
Lapierre
L. A.
,
Chew
C. S.
,
Goldenring
J. R.
(
1998
).
Rab11a redistributes to apical secretory canaliculus during stimulation of gastric parietal cells.
Am. J. Physiol
275
,
163
170
Casanova
J. E.
,
Wang
X.
,
Kumar
R.
,
Bhartur
S. G.
,
Navarre
J.
,
Woodrum
J. E.
,
Altschuler
Y.
,
Ray
G. S.
,
Goldenring
J. R.
(
1999
).
Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells.
Mol. Biol. Cell
10
,
47
61
Chavrier
P.
,
van der Sluijs
P.
,
Mishal
Z.
,
Nagelkerken
B.
,
Gorvel
J. P.
(
1997
).
Early endosome membrane dynamics characterized by flow cytometry.
Cytometry
29
,
41
49
Chen
W.
,
Feng
Y.
,
Chen
D.
,
Wandinger-Ness
A.
(
1998
).
Rab11 is required for trans-Golgi network-to-plasma membrane transport and a preferential target for GDP dissociation inhibitor.
Mol. Biol. Cell
9
,
3241
3257
Chiariello
M.
,
Bruni
C. B.
,
Bucci
C.
(
1999
).
The small GTPases Rab5a, Rab5b and Rab5c are differentially phosphorylated in vitro.
FEBS Lett
453
,
20
24
Christoforidis
S.
,
McBride
H. M.
,
Burgoyne
R. D.
,
Zerial
M.
(
1999
).
The Rab5 effector EEA1 is a core component of endosome docking.
Nature
397
,
621
625
Coimbra
T. M.
,
Furtado
M. R.
,
Lachat
J. J.
,
de Carvalho
I. F.
) (
1983
).
Effects of administration of cationic and native homologous albumin on the kidney.
Nephron
33
,
208
215
D'Arrigo
A.
,
Bucci
C.
,
Toh
B. H.
,
Stenmark
H.
(
1997
).
Microtubules are involved in bafilomycin A1-induced tubulation and Rab5-dependent vacuolation of early endosomes.
Eur. J. Cell Biol
72
,
95
103
Daro
E.
,
van der Sluijs
P.
,
Galli
T.
,
Mellman
I.
(
1996
).
Rab4 and cellubrevin define different early endosome populations on the pathway of transferrin receptor recycling.
Proc. Nat. Acad. Sci. USA
93
,
9559
9564
Davidson
H. W.
(
1995
).
Wortmannin causes mistargeting of procathepsin D. evidence for the involvement of a phosphatidylinositol 3-kinase in vesicular transport to lysosomes.
J. Cell Biol
130
,
797
805
Diaz
E.
,
Pfeffer
S. R.
(
1998
).
TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking.
Cell
93
,
433
443
Dirac-Svejstrup
A. B.
,
Sumizawa
T.
,
Pfeffer
S. R.
(
1997
).
Identification of a GDI displacement factor that releases endosomal Rab GTPases from Rab-GDI.
EMBO J
16
,
465
472
Duman
J. G.
,
Tyagarajan
K.
,
Kolsi
M. S.
,
Moore
H. P.
,
Forte
J. G.
(
1999
).
Expression of rab11a N124I in gastric parietal cells inhibits stimulatory recruitment of the H+-K+-ATPase.
Am. J. Physiol
277
,
361
–.
Echard
A.
,
Jollivet
F.
,
Martinez
O.
,
Lacapere
J. J.
,
Rousselet
A.
,
Janoueix-Lerosey
I.
,
Goud
B.
(
1998
).
Interaction of a Golgi-associated kinesin-like protein with Rab6.
Science
279
,
580
585
Feng
Y.
,
Press
B.
,
Wandinger-Ness
A.
(
1995
).
Rab 7: An important regulator of late endocytic membrane traffic.
J. Cell Biol
131
,
1435
1452
Finger
F. P.
,
Hughes
T. E.
,
Novick
P.
(
1998
).
Sec3p is a spatial landmark for polarized secretion in budding yeast.
Cell
92
,
559
571
Fitzgerald
M. L.
,
Reed
G. L.
(
1999
).
Rab6 is phosphorylated in thrombin-activated platelets by a protein kinase C-dependent mechanism: effects on GTP/GDP binding and cellular distribution.
Biochem. J
342
,
353
360
Ghosh
R. N.
,
Mallet
W. G.
,
Soe
T. T.
,
McGraw
T. E.
,
Maxfield
F. R.
(
1998
).
An endocytosed TGN38 chimeric protein is delivered to the TGN after trafficking through the endocytic recycling compartment in CHO cells.
J. Cell Biol
142
,
923
936
Goldenring
J. R.
,
Smith
J.
,
Vaughan
H. D.
,
Cameron
P.
,
Hawkins
W.
,
Navarre
J.
(
1996
).
Rab11 is an apically located small GTP-binding protein in epithelial tissues.
Am. J. Physiol
270
,
515
525
Gonzalez
L.
Jr.
,
Scheller
R. H.
(
1999
).
Regulation of membrane trafficking: Structural insights from a Rab/effector complex.
Cell
96
,
755
758
Gorvel
J. P.
,
Chavrier
P.
,
Zerial
M.
,
Gruenberg
J.
(
1991
).
RAB5 controls early endosome fusion in vitro.
Cell
64
,
915
925
Gournier
H.
,
Stenmark
H.
,
Rybin
V.
,
Lippe
R.
,
Zerial
M.
(
1998
).
Two distinct effectors of the small GTPase Rab5 cooperate in endocytic membrane fusion.
EMBO J
17
,
1930
1940
Gruenberg
J.
,
Griffiths
G.
,
Howell
K. E.
(
1989
).
Characterization of the early endosome and putative endocytic carrier vesicles in vivo and with an assay of vesicle fusion in vitro.
J. Cell Biol
108
,
1301
1316
Gruenberg
J.
,
Maxfield
F. R.
(
1995
).
Membrane transport in the endocytic pathway.
Curr. Opin. Cell Biol
7
,
552
563
Guo
W.
,
Roth
D.
,
Walch-Solimena
C.
,
Novick
P.
(
1999
).
The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis.
EMBO J
18
,
1071
1080
Harder
T.
,
Kellner
R.
,
Parton
R. G.
,
Gruenberg
J.
(
1997
).
Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol.
Mol. Biol. Cell
8
,
533
545
Horiuchi
H.
,
Lippe
R.
,
McBride
H. M.
,
Rubino
M.
,
Woodman
P.
,
Stenmark
H.
,
Rybin
V.
,
Wilm
M.
,
Ashman
K.
,
Mann
M.
, et al. 
(
1997
).
A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function.
Cell
90
,
1149
1159
Hunziker
W.
,
Peters
P. J.
(
1998
).
Rab17 localizes to recycling endosomes and regulates receptor-mediated transcytosis in epithelial cells.
J. Biol. Chem
273
,
15734
15741
Imamura
H.
,
Takaishi
K.
,
Nakano
K.
,
Kodama
A.
,
Oishi
H.
,
Shiozaki
H.
,
Monden
M.
,
Sasaki
T.
,
Takai
Y.
(
1998
).
Rho and Rab small G-proteins coordinately reorganize stress fibers and focal adhesions in MDCK cells.
Mol. Biol. Cell
9
,
2561
2575
Itin
C.
,
Ulitzur
N.
,
Muhlbauer
B.
,
Pfeffer
S. R.
(
1999
).
Mapmodulin, cytoplasmic dynein, and microtubules enhance the transport of mannose 6-phosphate receptors from endosomes to the trans-golgi network.
Mol. Biol. Cell
10
,
2191
2197
Jedd
G.
,
Mulholland
J.
,
Segev
N.
(
1997
).
Two new Ypt GTPases are required for exit from the yeast trans-Golgi compartment.
J. Cell Biol
137
,
563
580
Jones
S.
,
Jedd
G.
,
Kahn
R. A.
,
Franzusoff
A.
,
Bartolini
F.
,
Segev
N.
(
1999
).
Genetic interactions in yeast between Ypt GTPases and ARF guanine nucleotide exchangers.
Genetics
152
,
1543
1556
Kato
M.
,
Sasaki
T.
,
Ohya
T.
,
Nakanishi
H.
,
Nishioka
H.
,
Imamura
M.
,
Takai
Y.
(
1996
).
Physical and functional interaction of rabphilin-3A with alpha-actinin.
J. Biol. Chem
271
,
31775
31778
Knapp
P. E.
,
Swanson
J. A.
(
1990
).
Plasticity of the tubular lysosomal compartment in macrophages.
J. Cell Sci
95
,
433
439
Knight
A.
,
Hughson
E.
,
Hopkins
C. R.
,
Cutler
D. F.
(
1995
).
Membrane protein trafficking through the common apical endosome compartment of polarized Caco-2 cells.
Mol. Biol. Cell
6
,
597
610
Kurzchalia
T. V.
,
Gorvel
J. P.
,
Dupree
P.
,
Parton
R.
,
Kellner
R.
,
Houthaeve
T.
,
Gruenberg
J.
,
Simons
K.
(
1992
).
Interactions of Rab5 with cytosolic proteins.
J. Biol. Chem
267
,
18419
18423
Kutateladze
T. G.
,
Ogburn
K. D.
,
Watson
W. T.
,
de Beer
T.
,
Emr
S. D.
,
Burd
C. G.
,
Overduin
M.
(
1999
).
Phosphatidylinositol 3-phosphate recognition by the FYVE domain.
Mol. Cell
3
,
805
811
Lamaze
C.
,
Fujimoto
L. M.
,
Yin
H. L.
,
Schmid
S. L.
(
1997
).
The actin cytoskeleton is required for receptor-mediated endocytosis in mammalian cells.
J. Biol. Chem
272
,
20332
20335
Liu
K.
,
Li
G.
(
1998
).
Catalytic domain of the p120 Ras GAP binds to Rab5 and stimulates its GTPase activity.
J. Biol. Chem
273
,
10087
10090
Lombardi
D.
,
Soldati
T.
,
Riederer
M. A.
,
Goda
Y.
,
Zerial
M.
,
Pfeffer
S. R.
(
1993
).
Rab9 functions in transport between late endosomes and the trans-Golgi network.
EMBO J
12
,
677
682
Luan
P.
,
Balch
W. E.
,
Emr
S. D.
,
Burd
C. G.
(
1999
).
Molecular dissection of guanine nucleotide dissociation inhibitor function in vivo. Rab-independent binding to membranes and role of Rab recycling factors.
J. Biol. Chem
274
,
14806
14817
Lutcke
A.
,
Jansson
S.
,
Parton
R. G.
,
Chavrier
P.
,
Valencia
A.
,
Huber
L. A.
,
Lehtonen
E.
,
Zerial
M.
(
1993
).
Rab17, a novel small GTPase, is specific for epithelial cells and is induced during cell polarization.
J. Cell Biol
121
,
553
564
Lutcke
A.
,
Parton
R. G.
,
Murphy
C.
,
Olkkonen
V. M.
,
Dupree
P.
,
Valencia
A.
,
Simons
K.
,
Zerial
M.
(
1994
).
Cloning and subcellular localization of novel rab proteins reveals polarized and cell type-specific expression.
J. Cell Sci
107
,
3437
3448
Mallard
F.
,
Antony
C.
,
Tenza
D.
,
Salamero
J.
,
Goud
B.
,
Johannes
L.
(
1998
).
Direct pathway from early/recycling endosomes to the Golgi apparatus revealed through the study of Shiga toxin B-fragment transport.
J. Cell Biol
143
,
973
990
Mallet
W. G.
,
Maxfield
F. R.
(
1999
).
Chimeric forms of furin and TGN38 are transported with the plasma membrane in the trans-Golgi network via distinct endosomal pathways.
J. Cell Biol
146
,
345
359
Marsh
M.
,
McMahon
H. T.
(
1999
).
The structural era of endocytosis.
Science
285
,
215
220
Mayer
A.
,
Wickner
W.
(
1997
).
Docking of yeast vacuoles is catalyzedby the Ras-like GTPase Ypt7p after symmetric priming by Sec18p (NSF).
J. Cell Biol
136
,
307
317
McBride
H. M.
,
Rybin
V.
,
Murphy
C.
,
Giner
A.
,
Teasdale
R.
,
Zerial
M.
(
1999
).
Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13.
Cell
98
,
377
386
McLauchlan
H.
,
Newell
J.
,
Morrice
N.
,
Osborne
A.
,
West
M.
,
Smythe
E.
(
1998
).
A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits.
Curr. Biol
8
,
34
45
McMurtrie
E. B.
,
Barbosa
M. D.
,
Zerial
M.
,
Kingsmore
S. F.
(
1997
).
Rab17 and rab18, small GTPases with specificity for polarized epithelial cells: genetic mapping in the mouse.
Genomics
45
,
623
625
Mellman
I.
(
1996
).
Endocytosis and molecular sorting. Annu. Rev. Cell.
Dev. Biol
12
,
575
625
Meresse
S.
,
Gorvel
J. P.
,
Chavrier
P.
(
1995
).
The Rab7 GTPase resides on a vesicular compartment connected to lysosomes.
J. Cell Sci
108
,
3349
3358
Millar
C. A.
,
Powell
K. A.
,
Hickson
G. R.
,
Bader
M. F.
,
Gould
G. W.
(
1999
).
Evidence for a role for ADP-ribosylation factor 6 in insulin-stimulated glucose transporter-4 (GLUT4) trafficking in 3T3-L1 adipocytes [In Process Citation].
J. Biol. Chem
274
,
17619
17625
Mohrmann
K.
,
van der Sluijs
P.
(
1999
).
Regulation of membrane transport through the endocytic pathway by rabGTPases.
Mol. Membr. Biol
16
,
81
87
Mukherjee
S.
,
Ghosh
R. N.
,
Maxfield
F. R.
(
1997
).
Endocytosis.
Physiol. Rev.
77
,
759
803
Mukhopadhyay
A.
,
Funato
K.
,
Stahl
P. D.
(
1997
).
Rab7 regulates transport from early to late endocytic compartments in Xenopus oocytes.
J. Biol. Chem
272
,
13055
13059
Mullock
B. M.
,
Perez
J. H.
,
Kuwana
T.
,
Gray
S. R.
,
Luzio
J. P.
(
1994
).
Lysosomes can fuse with a late endosomal compartment in a cell-free system from rat liver.
J. Cell Biol
126
,
1173
1182
Mullock
B. M.
,
Bright
N. A.
,
Fearon
C. W.
,
Gray
S. R.
,
Luzio
J. P.
(
1998
).
Fusion of lysosomes with late endosomes produces a hybrid organelle of intermediate density and is NSF dependent.
J. Cell Biol
140
,
591
601
Murphy
C.
,
Saffrich
R.
,
Grummt
M.
,
Gournier
H.
,
Rybin
V.
,
Rubino
M.
,
Auvinen
P.
,
Lutcke
A.
,
Parton
R. G.
,
Zerial
M.
(
1996
).
Endosome dynamics regulated by a Rho protein.
Nature
384
,
427
432
Nakajima
Y.
,
Pfeffer
S. R.
(
1997
).
Phosphatidylinositol 3-kinase is not required for recycling of mannose 6-phosphate receptors from late endosomes to the trans-Golgi network.
Mol. Biol. Cell
8
,
577
582
Numata
S.
,
Shirataki
H.
,
Hagi
S.
,
Yamamoto
T.
,
Takai
Y.
(
1994
).
Phosphorylation of Rabphilin-3A, a putative target protein for Rab3A, by cyclic AMP-dependent protein kinase.
Biochem. Biophys. Res. Commun
203
,
1927
1934
Nuoffer
C.
,
Davidson
H. W.
,
Matteson
J.
,
Meinkoth
J.
,
Balch
W. E.
(
1994
).
A GDP-bound of Rab1 inhibits protein export from the endoplasmic reticulum and transport between Golgi compartments.
J. Cell Biol
125
,
225
237
Ohnishi
H.
,
Mine
T.
,
Shibata
H.
,
Ueda
N.
,
Tsuchida
T.
,
Fujita
T.
(
1999
).
Involvement of Rab4 in regulated exocytosis of rat pancreatic acini.
Gastroenterology
116
,
943
952
Ohya
T.
,
Sasaki
T.
,
Kato
M.
,
Takai
Y.
(
1998
).
Involvement of Rabphilin3 in endocytosis through interaction with Rabaptin5.
J. Biol. Chem
273
,
613
617
Olkkonen
V. M.
,
Dupree
P.
,
Killisch
I.
,
Lutcke
A.
,
Zerial
M.
,
Simons
K.
(
1993
).
Molecular cloning and subcellular localization of three GTP-binding proteins of the Rab subfamily.
J. Cell Sci
106
,
1249
1261
Parton
R. G.
,
Schrotz
P.
,
Bucci
C.
,
Gruenberg
J.
(
1992
).
Plasticity of early endosomes.
J. Cell Sci
103
,
335
348
Patki
V.
,
Virbasius
J.
,
Lane
W. S.
,
Toh
B. H.
,
Shpetner
H. S.
,
Corvera
S.
(
1997
).
Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase.
Proc. Nat. Acad. Sci. USA
94
,
7326
7330
Peränen
J.
,
Auvinen
P.
,
Virta
H.
,
Wepf
R.
,
Simons
K.
(
1996
).
Rab8 promotes polarized membrane transport through reorganization of actin and microtubules in fibroblasts.
J. Cell Biol
135
,
153
167
Peterson
M. R.
,
Burd
C. G.
,
Emr
S. D.
(
1999
).
Vac1p coordinates Raband phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome.
Curr. Biol
9
,
159
162
Pfeffer
S. R.
,
Dirac-Svejstrup
A. B.
,
Soldati
T.
(
1995
).
Rab GDP dissociation inhibitor: putting rab GTPases in the right place.
J. Biol. Chem
270
,
17057
17059
Pierre
P.
,
Scheel
J.
,
Rickard
J. E.
,
Kreis
T. E.
(
1992
).
CLIP-170 links endocytic vesicles to microtubules.
Cell
70
,
887
900
Raposo
G.
,
Cordonnier
M. N.
,
Tenza
D.
,
Menichi
B.
,
Durrbach
A.
,
Louvard
D.
,
Coudrier
E.
(
1999
).
Association of myosin I alpha with endosomes and lysosomes in mammalian cells.
Mol. Biol. Cell
10
,
1477
1494
Reaves
B. J.
,
Bright
N. A.
,
Mullock
B. M.
,
Luzio
J. P.
(
1996
).
The effect of wortmannin on the localisation of lysosomal type I integral membrane glycoproteins suggests a role for phosphoinositide 3-kinase activity in regulating membrane traffic late in the endocytic pathway.
J. Cell Sci
109
,
749
762
Ren
M.
,
Zeng
J.
,
De Lemos-Chiarandini
C.
,
Rosenfeld
M.
,
Adesnik
M.
,
Sabatini
D. D.
(
1996
).
In its active form, the GTP-binding protein Rab8 interacts with a stress-activated protein kinase.
Proc. Nat. Acad. Sci. USA
93
,
5151
5155
Ren
M.
,
Xu
G.
,
Zeng
J.
,
De Lemos-Chiarandini
C.
,
Adesnik
M.
,
Sabatini
D. D.
(
1998
).
Hydrolysis of GTP on Rab11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes.
Proc. Nat. Acad. Sci. USA
95
,
6187
6192
Riederer
M. A.
,
Soldati
T.
,
Shapiro
A. D.
,
Lin
J.
,
Pfeffer
S. R.
(
1994
).
Lysosome biogenesis requires Rab9 function and receptor recycling from endosomes to the trans-Golgi network.
J. Cell Biol
125
,
573
582
Riezman
H.
,
Munn
A.
,
Geli
M. I.
,
Hicke
L.
(
1996
).
Actin-, myosin-and ubiquitin-dependent endocytosis.
Experientia
52
,
1033
1041
Santama
N.
,
Krijnse-Locker
J.
,
Griffiths
G.
,
Noda
Y.
,
Hirokawa
N.
,
Dotti
C. G.
(
1998
).
KIF2beta, a new kinesin superfamily protein in non-neuronal cells, is associated with lysosomes and may be implicated in their centrifugal translocation.
EMBO J
17
,
5855
5867
Sapperstein
S. K.
,
Lupashin
V. V.
,
Schmitt
H. D.
,
Waters
M. G.
(
1996
).
Assembly of the ER to Golgi SNARE complex requires Uso1p.
J. Cell Biol
132
,
755
767
Sasaki
T.
,
Shirataki
H.
,
Nakanishi
H.
,
Takai
Y.
(
1997
).
Rab3A-rabphilin-3A system in neurotransmitter release.
Advan. Second Messenger Phosphoprotein Res
31
,
279
294
Sato
K.
,
Wickner
W.
(
1998
).
Functional reconstitution of Ypt7p GTPase and a purified vacuole SNARE complex.
Science
281
,
700
702
Schimmöller
F.
,
Simon
I.
,
Pfeffer
S. R.
(
1998
).
Rab GTPases, directors of vesicle docking.
J. Biol. Chem
273
,
22161
22164
Sheetz
M. P.
(
1999
).
Motor and cargo interactions.
Eur. J. Biochem
262
,
19
25
Sheff
D. R.
,
Daro
E. A.
,
Hull
M.
,
Mellman
I.
(
1999
).
The receptor recycling pathway contains two distinct populations of early endosomes with different sorting functions.
J. Cell Biol
145
,
123
139
Shirataki
H.
,
Kaibuchi
K.
,
Sakoda
T.
,
Kishida
S.
,
Yamaguchi
T.
,
Wada
K.
,
Miyazaki
M.
,
Takai
Y.
(
1993
).
Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin.
Mol. Cell Biol
13
,
2061
2068
Shpetner
H.
,
Joly
M.
,
Hartley
D.
,
Corvera
S.
(
1996
).
Potential sites of PI-3 kinase function in the endocytic pathway revealed by the PI-3 kinase inhibitor, wortmannin.
J. Cell Biol
132
,
595
605
Siddhanta
U.
,
McIlroy
J.
,
Shah
A.
,
Zhang
Y.
,
Backer
J. M.
(
1998
).
Distinct roles for the p110alpha and hVPS34 phosphatidylinositol 3-kinases in vesicular trafficking, regulation of the actin cytoskeleton, and mitogenesis.
J. Cell Biol
143
,
1647
1659
Simon
V. R.
,
Pon
L. A.
(
1996
).
Actin-based organelle movement.
Experientia
52
,
1117
1122
Simonsen
A.
,
Lippe
R.
,
Christoforidis
S.
,
Gaullier
J. M.
,
Brech
A.
,
Callaghan
J.
,
Toh
B. H.
,
Murphy
C.
,
Zerial
M.
,
Stenmark
H.
(
1998
).
EEA1 links PI(3)K function to Rab5 regulation of endosome fusion.
Nature
394
,
494
498
Soldati
T.
,
Shapiro
A. D.
,
Svejstrup
A. B.
,
Pfeffer
S. R.
(
1994
).
Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange.
Nature
369
,
76
78
Sönnichsen
B.
,
Zerial
M.
(
1998
).
Membrane dynamics of the perinuclear recycling endosome monitored with Rab11-GFP.
Mol. Biol. Cell
9
,
464
–.
Stenmark
H.
,
Valencia
A.
,
Martinez
O.
,
Ullrich
O.
,
Goud
B.
,
Zerial
M.
(
1994
).
Distinct structural elements of Rab5 define its functional specificity.
EMBO J
13
,
575
583
Stenmark
H.
,
Vitale
G.
,
Ullrich
O.
,
Zerial
M.
(
1995
).
Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion.
Cell
83
,
423
432
Stenmark
H.
,
Aasland
R.
(
1999
).
FYVE-finger proteins: effectors of an inositol lipid.
J. Cell Sci.
Ullrich
O.
,
Reinsch
S.
,
Urbe
S.
,
Zerial
M.
,
Parton
R. G.
(
1996
).
Rab11 regulates recycling through the pericentriolar recycling endosome.
J. Cell Biol
135
,
913
924
Ungermann
C.
,
Sato
K.
,
Wickner
W.
(
1998
).
Defining the functions of trans-SNARE pairs.
Nature
396
,
543
548
Urbe
S.
,
Huber
L. A.
,
Zerial
M.
,
Tooze
S. A.
,
Parton
R. G.
(
1993
).
Rab11, a small GTPase associated with both constitutive and regulated secretory pathways in PC12 cells.
FEBS Lett
334
,
175
182
van der Sluijs
P.
,
Hull
M.
,
Huber
L. A.
,
Male
P.
,
Goud
B.
,
Mellman
I.
(
1992
).
Reversible phosphorylation—dephosphorylation determines the localization of rab4 during the cell cycle.
EMBO J
11
,
4379
4389
Vitale
G.
,
Rybin
V.
,
Christoforidis
S.
,
Thornqvist
P.
,
McCaffrey
M.
,
Stenmark
H.
,
Zerial
M.
(
1998
).
Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound Rab4 and Rab5.
EMBO J
17
,
1941
1951
Vitelli
R.
,
Santillo
M.
,
Lattero
D.
,
Chiariello
M.
,
Bifulco
M.
,
Bruni
C. B.
,
Bucci
C.
(
1997
).
Role of the small GTPase Rab7 in the late endocytic pathway.
J. Biol. Chem
272
,
4391
4397
Ward
D. M.
,
Leslie
J. D.
,
Kaplan
J.
(
1997
).
Homotypic lysosome fusion in macrophages: analysis using an in vitro assay.
J. Cell Biol
139
,
665
673
Witke
W.
,
Podtelejnikov
A. V.
,
Di Nardo
A.
,
Sutherland
J. D.
,
Gurniak
C. B.
,
Dotti
C.
,
Mann
M.
(
1998
).
In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly.
EMBO J
17
,
967
976
Wu
S. K.
,
Zeng
K.
,
Wilson
I. A.
,
Balch
W. E.
(
1996
).
Structural insights into the function of the Rab GDI superfamily.
Trends Biochem. Sci
21
,
472
476
Wurmser
A. E.
,
Gary
J. D.
,
Emr
S. D.
(
1999
).
Phosphoinositide 3-kinases and their FYVE domain-containing effectors as regulators of vacuolar/lysosomal membrane trafficking pathways.
J. Biol. Chem
274
,
9129
9132
Xiao
G. H.
,
Shøarinejad
F.
,
Jin
F.
,
Golemis
E. A.
,
Yeung
R. S.
(
1997
).
The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis.
J. Biol. Chem
272
,
6097
6100
Xu
X.
,
Press
B.
,
Wagle
N. M.
,
Cho
H.
,
Wandinger-Ness
A.
,
Pierce
S. K.
(
1996
).
B cell antigen receptor signaling links biochemical changes in the class II peptide-loading compartment to enhanced processing.
Int. Immunol
8
,
1867
1876
Xu
Z.
,
Sato
K.
,
Wickner
W.
(
1998
).
LMA1 binds to vacuoles at Sec18p (NSF), transfers upon ATP hydrolysis to a t-SNARE (Vam3p) complex, and is released during fusion.
Cell
93
,
1125
1134
Zacchi
P.
,
Stenmark
H.
,
Parton
R. G.
,
Orioli
D.
,
Lim
F.
,
Giner
A.
,
Mellman
I.
,
Zerial
M.
,
Murphy
C.
(
1998
).
Rab17 regulates membrane trafficking through apical recycling endosomes in polarized epithelial cells.
J. Cell Biol
140
,
1039
1053
Zeng
J.
,
Ren
M.
,
Gravotta
D.
,
De Lemos-Chiarandini
C.
,
Lui
M.
,
Erdjument-Bromage
H.
,
Tempst
P.
,
Xu
G.
,
Shen
T. H.
,
Morimoto
T.
,
Adesnik
M.
,
Sabatini
D. D.
(
1999
).
Identification of a putative effector protein for Rab11 that participates in transferrin recycling.
Proc. Nat. Acad. Sci. USA
96
,
2840
2845
Zuk
P. A.
,
Elferink
L. A.
(
1999
).
Rab15 mediates an early endocytic event in Chinese hamster ovary cells.
J. Biol. Chem
274
,
22303
22312
This content is only available via PDF.