Glycoproteins that inhibit neurite outgrowth may guide growth cones during development by acting as a barrier and closing off inappropriate routes. Their continued expression in the adult central nervous system may be a key factor in preventing regeneration of central nervous system neurons. A glycoprotein of 55 kDa has been isolated from the detergent-insoluble membrane skeleton from adult chicken brain. Initial experiments showed that dorsal root ganglion neurons would not adhere to or extend neurites on a substratum coated with GP55. Furthermore, GP55 will act as a barrier to the advance of established growth cones in the presence of poly-L-lysine, laminin or G4. Central nervous system neurons from forebrain as well as dorsal root ganglion neurons from the peripheral nervous system are inhibited by GP55. GP55 is also effective in blocking the initial adhesion of neurons to a substratum of poly-L-lysine and, particularly, laminin. In contrast to the inhibition of neurite outgrowth, neuronal adhesion is concentration independent over the range tested. A preliminary investigation of the mechanism by which GP55 inhibits outgrowth suggests that a pertussis toxin-sensitive G protein is required. Preliminary evidence suggests that GP55 is anchored in the membrane by a glycosyl phosphatidylinositol moiety. GP55 is distinct from previously identified inhibitory proteins, based on the source and molecular mass, and is thus a new member of this rapidly expanding family.

REFERENCES

Aizenman
Y.
,
Weichsel
M. E.
,
De Vellis
J.
(
1986
).
Changes in insulin and transferrin requirements of pure brain neuronal cultures during embryonic development.
Proc. Nat. Acad. Sci. USA
83
,
2263
2266
Allsopp
T. E.
,
Moss
D. J.
(
1989
).
A developmentally regulated chicken neuronal protein associated with the cortical cytoskeleton.
J. Neurosci
9
,
13
24
Baird
D. H.
,
Baptista
C. A.
,
Wang
L. C.
,
Mason
C. A.
(
1992
).
Specificity of a target cell-derived stop signal for afferent axonal growth.
J. Neurobiol
23
,
579
591
Baird
J. L.
,
Raper
J. A.
(
1992
).
The repulsion of retinal growth cones by peripheral neurites is reduced by a serine protease inhibitor. Mol. Biol.
Cell
3
,
191
–.
Bandtlow
C. E.
,
Schmidt
M. F.
,
Hassinger
T. D.
,
Schwab
M. E.
,
Kater
S. B.
(
1993
).
Role of intracellular calcium in NI-35-evoked collapse of neuronal growth cones.
Science
259
,
80
83
Berman
S. A.
,
Moss
D.
,
Bursztajn
S.
(
1993
).
Axonal branching and growth cone structure depend on target cells.
Dev. Biol
159
,
153
162
Berridge
M. J.
(
1993
).
Inositol trisphosphate and calcium signalling.
Nature
361
,
315
325
Bixby
J. L.
,
Zhang
R.
(
1990
).
Purified N-cadherin is a potent substratum for the rapid induction of neurite outgrowth.
J. Cell Biol
110
,
1253
1260
Brummendorf
T.
,
Wolff
J. M.
,
Frank
R.
,
Rathjen
F. G.
(
1989
).
Neural cell recognition molecule F11: homology with fibronectin type III and immunoglobulin type C domains.
Neuron
2
,
1351
1361
Brummendorf
T.
,
Hubert
M.
,
Treubert
U.
,
Leuschner
R.
,
Tarnok
A.
,
Rathjen
F. G.
(
1993
).
The axonal recognition molecule F11 is a multifunctional protein; specific domains mediate interactions with Ng-CAM and restrictin.
Neuron
10
,
711
727
Caroni
P.
,
Schwab
M. E.
(
1988
).
Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substratum properties of CNS white matter.
Neuron
1
,
85
96
Clarke
G. A.
,
White
C. A.
,
Moss
D. J.
(
1993
).
Substrate-bound GP130/F11 will promote neurite outgrowth: evidence for a cell surface receptor.
Eur. J. Cell Biol
61
,
108
115
Cooper
M. W.
,
Smith
S. J.
(
1992
).
A real time analysis of growth cone-target cell intereactions during the formation of stable contacts between hippocampal neurons in culture.
J. Neurobiol
23
,
814
828
Davies
J. A.
,
Cook
G. M.
,
Stern
C. D.
,
Keynes
R. J.
(
1990
).
Isolation from chick somites of a glycoprotein fraction that causes collapse of dorsal root ganglion growth cones.
Neuron
4
,
11
20
Durbec
P.
,
Gennarini
G.
,
Goridis
C.
,
Rougon
G.
(
1992
).
A soluble form of the F3 Neuronal cell adhesion molecule promotes neurite outgrowth.
J. Cell Biol
117
,
877
888
Igarashi
M.
,
Strittmatter
S. M.
,
Vartanian
T.
,
Fishman
M. C.
(
1993
).
Mediation by proteins of signals that cause collapse of growth cones.
Science
259
,
77
79
Ivins
J. K.
,
Raper
J. A.
,
Pittman
R. N.
(
1991
).
Intracellular calcium levels do not change during contact-mediated collapse of chick DRG growth cone structure.
J. Neurosci
11
,
1597
1608
Kapfhammer
J. P.
,
Schwab
M. E.
(
1992
).
Modulators of neuronal migration and neurite growth.
Curr. Opin. Cell Biol
4
,
863
868
Kaziro
Y.
,
Itoh
H.
,
Kozasa
T.
,
Nakafuku
M.
,
Satoh
T.
(
1991
).
Structure and function of signal-transducing GTP-binding proteins.
Annu. Rev. Biochem
60
,
349
400
Keynes
R. J.
,
Stern
C. D.
(
1984
).
Segmentation in the vertebrate nervous system.
Nature
310
,
786
789
Keynes
R.
,
Cook
G.
(
1990
).
Cell-cell repulsion: Clues from the growth cone?.
Cell
62
,
609
610
Kuhn
T. B.
,
Stoeckli
E. T.
,
Condrau
M. A.
,
Rathjen
F. G.
,
Sonderegger
P.
(
1991
).
Neurite outgrowth on immobilized axonin-1 is mediated by a heterophilic interaction with L1(G4).
J. Cell Biol
115
,
1113
1126
Lagenaur
C.
,
Lemmon
V.
(
1987
).
An L1-like molecule, the 8D9 antigen, is a potent substratum for neurite extension.
Proc. Nat. Acad. Sci. USA
84
,
7753
7757
Lander
A. D.
,
Fujii
D. K.
,
Reichardt
L. F.
(
1985
).
Purification of a factor that promotes neurite outgrowth: isolation of laminin and associated molecules.
J. Cell Biol
101
,
893
913
Lemmon
V.
,
Burden
S. M.
,
Payne
H. R.
,
Elmslie
G. J.
,
Hlavin
M. L.
(
1992
).
Neurite growth on different substrata: permissive versus instructive influences and the role of adhesive strength.
J. Neurosci
12
,
818
826
Luo
Y.
,
Raible
D.
,
Raper
J. A.
(
1993
).
Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones.
Cell
75
,
217
227
Matsudaira
P.
,
Burgess
D. R.
(
1978
).
SDS microslab linear gradient polyacrylamide gel electrophoresis.
Anal. Biochem
87
,
386
396
Morrisey
J. A.
(
1981
).
Silver stain for proteins in polyacrylamide gels: a modified procedure with enhanced sensitivity.
Anal. Biochem
117
,
307
310
Moss
D. J.
,
White
C. A.
(
1992
).
Solubility and posttranslational regulation of GP130/F11- a neuronal GPI-linked cell adhesion molecule enriched in the neuronal membrane skeleton.
Eur. J. Cell Biol
57
,
59
65
Oakley
R. A.
,
Tosney
K. W.
(
1991
).
Peanut agglutinin and chondroitin-6-sulphate are molecular markers for tissues that act as barriers to axon advance in the avian embryo.
Dev. Biol
147
,
187
206
Pesheva
P.
,
Gennarini
G.
,
Goridis
C.
,
Schachner
M.
(
1993
).
The F3/F11 cell adhesion molecule mediates the repulsion of neurons by the extracellular matrix glycoprotein J1-160/180.
Neuron
10
,
69
82
Raper
J. A.
,
Kapfhammer
J. P.
(
1990
).
The enrichment of a neuronal growth cone collapsing activity from embryonic chick brain.
Neuron
2
,
21
29
Rodriguez
J.
,
Deinhard
F.
(
1960
).
Preparation of a semipermanent mounting medium for fluorescent antibody studies.
Virology
12
,
316
317
Rogers
S. L.
,
Letourneau
P. C.
,
Palm
S. L.
,
McCarthy
J.
,
Furcht
L.R.
) (
1983
).
Neurite extension by peripheral and central nervous system neurons in response to substratum-bound fibronectin and laminin.
Dev. Biol
98
,
212
220
Schnell
L.
,
Schwab
M. E.
(
1990
).
Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors.
Nature
343
,
269
272
Schnell
L.
,
Schneider
R.
,
Kolbeck
R.
,
Barde
Y.-A.
,
Schwab
M. E.
) (
1994
).
Neurotrophin-3 enhances sprouting of corticospinal tract during development and after spinal cord lesion.
Nature
367
,
170
173
Snow
D. M.
,
Steindler
D. A.
,
Silver
J.
(
1990
).
Molecular and cellular characterisation of the glial roof plate of the spinal cord and optic tectum: a possible role for a proteoglycan in the development of an axon barrier.
Dev. Biol
138
,
359
376
Stahl
B.
,
Muller
B.
,
von-Boxberg
Y.
,
Cox
E. C.
,
Bonhoeffer
F.
(
1990
).
Biochemical characterization of a putative axonal guidance molecule of the chick visual system.
Neuron
5
,
735
743
Strittmatter
S. M.
,
Valenzuela
D.
,
Kennedy
T. E.
,
Neerm
E. J.
,
Fishman
M. C.
(
1990
).
G0 is a major growth cone protein subject to regulation by GAP-43.
Nature
344
,
836
841
Vestal
D. J.
,
Ranscht
B.
(
1992
).
Glycosyl phosphatidylinositol-anchored T-cadherin mediates calcium-dependent, homophilic cell adhesion.
J. Cell Biol
119
,
451
461
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