Periaxin is a newly described protein that is expressed exclusively by myelinating Schwann cells. In developing nerves, periaxin is first detected as Schwann cells ensheathe axons, prior to the appearance of the proteins that characterize the myelin sheath. Periaxin is initially concentrated in the adaxonal membrane (apposing the axon) but, during development, as myelin sheaths mature, periaxin becomes predominately localized at the abaxonal Schwann cell membrane (apposing the basal lamina). In permanently axotomized adult nerves, periaxin is lost from the abaxonal and adaxonal membranes, becomes associated with degenerating myelin sheaths and is phagocytosed by macrophages. In crushed nerves, in which axons regenerate and are remyelinated, periaxin is first detected in the adoxonal membrane as Schwann cells ensheathe regenerating axons, but again prior to the appearance of other myelin proteins. Periaxin mRNA and protein levels change in parallel with those of other myelin-related genes after permanent axotomy and crush. These data demonstrate that periaxin is expressed by myelinating Schwann cells in a dynamic, developmentally regulated manner. The shift in localization of periaxin in the Schwann cell after completion of the spiralization phase of myelination suggests that periaxin participates in membrane-protein interactions that are required to stabilize the mature myelin sheath.

Reference

Aguayo
A. J.
,
Bray
G. M.
,
Terry
L. C.
,
Sweezey
E.
(
1976
)
Three-dimensional analysis of unmyelinated fibers in normal and pathologic autonomic nerves.
J. Neuropathol. Exp. Neurol
35
,
136
151
Aguayo
A. J.
,
Chavron
L.
,
Bray
G. M.
(
1976
)
Potential of Schwann cells from unmyelinated nerves to produce myelin: A quantitative ultrastructural and radiographic study.
J. Neurocytol
5
,
565
573
Apostolski
S.
,
Sadiq
S. A.
,
Hays
A.
,
Corbo
M.
,
Suturkova
L.
,
Chaliff
P.
,
Stefansson
K.
,
LeBaron
R. G.
,
Ruoslahti
E.
,
Hays
A. P.
,
Latov
N.
(
1994
)
Identification of Gal(1–3)GalNAc bearing glycoproteins at the nodes of Ranvier in peripheral nerve.
J. Neurosci. Res
38
,
134
141
Archelos
J. J.
,
Roggenbuck
K.
,
Schneider-Schaulies
J.
,
Linington
C.
,
Toyka
K. V.
,
Hartung
H. P.
(
1993
)
Production and characterization of monoclonal antibodies to the extracellular domain of PO.
J. Neurosci. Res
35
,
46
53
Bergoffen
J.
,
Scherer
S. S.
,
Wang
S.
,
Oronzi-Scott
M.
,
Bone
L.
,
Paul
D. L.
,
Chen
K.
,
Lensch
M. W.
,
Chance
P.
,
Fischbeck
K.
(
1993
)
Connexin mutations in X-linked Charcot-Marie-Tooth disease.
Science
262
,
2039
2042
Berryman
M. A.
,
Porter
W. R.
,
Rodewald
R. D.
,
Hubbard
A. L.
(
1992
)
Effects of tannic acid on antigenicity and membrane contrast in ultrastructural immunocytochemistry.
J. Histochem. Cytochem
40
,
845
857
Chirgwin
J. M.
,
Przbyla
A. E.
,
MacDonald
R. J.
,
Rutter
R. J.
(
1979
)
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
Biochem
18
,
5294
5299
Clark
M. B.
,
Bunge
M. B.
(
1989
)
Cultured Schwann cells assemble normal-appearing basal laminae only when they ensheathe axons.
Dev. Biol
133
,
393
404
Curtis
R.
,
Stewart
H. J. S.
,
Hall
S. M.
,
Wilkin
G. P.
,
Mirsky
R.
,
Jessen
K. R.
(
1992
)
GAP-43 is expressed by nonmyelin-forming Schwann cells of the peripheral nervous system.
J. Cell Biol
116
,
1455
1464
Dieperink
M. E.
,
Oneill
A.
,
Magnoni
G.
,
Wollmann
R. L.
,
Heinrikson
R. L.
,
Zurcherneely
H. A.
,
Stefansson
K.
(
1992
)
SAG- a Schwann cell membrane glycoprotein.
J. Neurosci
12
,
2177
2185
Dijkstra
C. D.
,
Doop
E. A.
,
Joling
P.
,
Kraal
G.
(
1985
)
The heterogeneity of mononuclear phogocytes in lymphoid organs: distinct macrophage subpopulations in the reat recognized by monoclonal antibodies ED1, ED2 and ED3.
Immunol
54
,
589
600
Dubois-Dalcq
M.
,
Behar
T.
,
Lazzarini
R. A.
(
1987
)
Emergence of three myelin proteins in oligodendrocytes cultured without neurons.
J. Cell Biol
102
,
384
392
Einheber
S.
,
Milner
T.
,
Giancotti
F.
,
Salzer
J.
(
1993
)
Axonal regulation of Schwann cell integrin expresssion suggests a role for6 4 in myelination.
J. Cell Biol
123
,
625
638
Eldridge
C. F.
,
Bunge
M. B.
,
Bunge
R. P.
(
1989
)
Differentiation of axon-related Schwann cell in vitro: II. Control of myelin formation by basal lamina.
J. Neurosci
9
,
625
638
Eldridge
C. F.
,
Bunge
M. B.
,
Bunge
R. P.
,
Wood
P. M.
(
1987
)
Differentiation of axon-related Schwann cells in vitro. I. Ascorbic acid regulates basal laminia assembly and myelin formation.
J. Cell Biol
105
,
1023
1034
Fannon
A. M.
,
Sherman
D. L.
,
Ilyina-Gragerova
G.
,
Brophy
P. J.
,
Friedrich
V. L.
,
Colman
D. R.
(
1995
)
Novel E-cadherin mediated adhesion in peripheral nerve: Schwann cell architecture is stabilized by autotypic adherens junctions.
J. Cell Biol
129
,
189
202
Feltri
M. L.
,
Scherer
S. S.
,
Nemni
R.
,
Kamholz
J.
,
Vogelbacker
H.
,
Oronzi-Scott
M.
,
Canal
N.
,
Quaranta
V.
,
Wrabetz
L.
(
1994
)
4 integrin expression in myelinating Schwann cells is ab-axonally polarized, developmentally-regulated, and axonally-dependent.
Development
120
,
1287
1301
Fernandez-Valle
C.
,
Fregien
N.
,
Wood
P. M.
,
Bunge
M. B.
(
1993
)
Expression of the protein zero myelin gene in axon-related Schwann cells is linked to basal lamina formation.
Development
119
,
867
880
Fort
P.
,
Marty
L.
,
Piechaczyk
M.
,
Sabrouty
S. E.
,
Dani
C.
,
Jeanteur
P.
,
Blanchard
J. M.
(
1985
)
Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family.
Nucl. Acids Res
13
,
1431
1442
Gillespie
C. S.
,
Sherman
D. L.
,
Blair
G. E.
,
Brophy
P. J.
(
1994
)
Periaxin, a novel protein of myelinating Schwann cells with a possible role in axonal ensheathment.
Neuron
12
,
497
508
Grinspan
J.
,
Wrabetz
L.
,
Kamholz
J.
(
1993
)
Oligodendrocyte maturation and myelin gene expression in PDGF-treated cultures from rat cerebral white matter.
J. Neurocytol
22
,
322
333
Gupta
S. K.
,
Pringle
J.
,
Poduslo
J. F.
,
Mezei
C.
(
1993
)
Induction of myelin genes during peripheral nerve remyelination requires a continuous signal from the ingrowing axon.
J. Neurosci. Res
34
,
14
23
Hahn
A. F.
,
Whitaker
J. N.
,
Kachar
B.
,
Webster
H. d.
(
1987
)
P2, P1, and P0 myelin basic protein expression in developing rat sixth nerve: a quantitative immunocytochemical study.
J. Comp. Neurol
260
,
501
512
Lamperth
L.
,
Manuelidis
L.
,
Webster
H. d.
(
1990
)
P0 glycoprotein: messenger RNA distribution in myelin-forming Schwann cells at the developing rat trigeminal ganglion.
J. Neurocytol
19
,
756
769
Langley
J. N.
,
Anderson
H. K.
(
1903
)
On the union of the fifth cervical nerve with the superior cervical ganglion.
J. Physiol
30
,
439
442
Lemke
G.
(
1993
)
The molecular genetics of myelination- an update.
Glia
7
,
263
271
Lemke
G.
,
Axel
R.
(
1985
)
Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin.
Cell
40
,
501
508
Li
C.
,
Topak
M. B.
,
Gerial
R.
,
Calpoff
S.
,
Abramow-Newerly
W.
,
Trapp
B.
,
Peterson
A.
,
Roder
J.
(
1994
)
Myelination in the absence of myelin-associated glycoprotein.
Nature
369
,
747750
–.
Martini
R.
,
Bollensen
E.
,
Schnachner
M.
(
1988
)
Immunocytological localization of the major peripheral nervous system glycoprotein P0 and the L2/HNK-1 and L3 carbohydrate structures in developing and adult mouse sciatic nerve.
Dev. Biol
129
,
330
338
Martini
R.
,
Schachner
M.
(
1986
)
Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and MAG) and their shared carbohydrates epitope and myelin basic protein in developing sciatic nerve.
J. Cell Biol
103
,
2434
2448
Martini
R.
,
Schachner
M.
(
1988
)
Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and myelin-associated glycoprotein) in regenerating adult mouse sciatic nerve.
J. Cell Biol
106
,
1735
1746
McLean
I. W.
,
Nakane
P. K.
(
1974
)
Periodate-lysine paraformaldehyde fixative: A new fixative for immunoelectron microscopy.
J. Histochem. Cytochem
22
,
1077
1083
Montag
D.
,
Giese
K. P.
,
Bartsch
U.
,
Martini
R.
,
Lang
Y.
,
Bluthmann
H.
,
Karthigasan
J.
,
Kirschner
D. A.
,
Wintergerst
E. S.
,
Nave
K.-A.
,
Zielasek
J.
,
Toyka
K. V.
,
Lipp
H.-P.
,
Schachner
M.
(
1994
)
Mice deficient for the myelin-associated glycoprotein show subtle abnormalities in myelin.
Neuron
13
,
229
246
Owens
G. C.
,
Bunge
R. P.
(
1989
)
Evidence for an early role of myelin-associated glycoprotein in the process of myelination.
Glia
2
,
119
128
Plantinga
L. C.
,
Verhaagen
J.
,
Edwards
P. M.
,
Hol
E. M.
,
Bar
P. R.
,
Gispen
W. H.
(
1993
)
The expression of B-50/GAP-43 in Schwann cells is upregulated in degenerating peripheral nerve stumps following nerve injury.
Brain Res
602
,
69
76
Radeke
M. J.
,
Misko
T. P.
,
Hsu
C.
,
Herzenberg
L. A.
,
Shooter
E. M.
(
1987
)
Gene transfer and molecular cloning of the rat nerve growth factor receptor.
Nature
325
,
593
597
Scherer
S. S.
,
Wang
D.-y.
,
Kuhn
R.
,
Lemke
G.
,
Wrabetz
L.
,
Kamholz
J.
(
1994
)
Axons regulate Schwann cell expression of the POU transcription factor SCIP.
J. Neurosci
14
,
1930
1942
Scherer
S. S.
,
Xu
Y.-T.
,
Roling
D.
,
Wrabetz
L.
,
Feltri
M. L.
,
Kamholz
J.
(
1994
)
Expression of growth-associated protein-43 kD in Schwann cells is regulated by axon-Schwann cell interactions and cAMP.
J. Neurosci. Res
38
,
575
589
Schreyer
D. J.
,
Skene
J. H. P.
(
1991
)
Fate of GAP-43 in ascending spinal axons of DRG neurons after peripheral nerve injury- delayed accumulation and correlation with regenerative potential.
J. Neurosci
11
,
3738
3751
Shuman
S.
,
Hardey
M.
,
Pleasure
D.
(
1986
)
Immunochemical characterization of peripheral nervous system myelin 170,000-Mrglycoprotein.
J. Neurochem
47
,
811
818
Simpson
S. A.
,
Young
J. Z.
(
1945
)
Regeneration of fibre diameter after cross-union of visceral and somatic nerves.
J. Anat
79
,
48
65
Snipes
G. J.
,
Suter
U.
,
Welcher
A. A.
,
Shooter
E. M.
(
1992
)
Characterization of a novel peripheral nervous system myelin protein (PMP-22/SR13).
J. Cell Biol
117
,
225
238
Sternberger
N. H.
,
Quarles
R. H.
,
Itoyama
Y.
,
Webster
H. d.
(
1979
)
Myelin-associated glycoprotein demonstrated immunocytochemically in myelin and myelin-forming cells of developing rat.
Proc. Natl. Acad. Sci. USA
76
,
1510
1514
Stoll
G.
,
Griffin
J. W.
,
Li
C. Y.
,
Trapp
B. D.
(
1989
)
Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation.
J. Neurocytol
18
,
671
683
Taniuchi
M.
,
Clark
H. B.
,
Schweitzer
J. B.
,
Johnson
E. M.
Jr
(
1988
)
Expression of nerve growth factor receptors by Schwann cells of axotomized peripheral nerves: Ultrastructural location, suppression by axonal contact, and binding properties.
J. Neurosci
8
,
664
681
Trapp
B. D.
,
Andrews
S. B.
,
Wong
A.
,
O'Connell
M.
,
Griffin
J. W.
(
1989
)
Co-localization of the myelin-associated glycoprotein and the microfilament components, F-actin and spectrin, in Schwann cells of myelinated nerve fibers.
J. Neurocytol
18
,
47
60
Trapp
B. D.
,
Quarles
R. H.
(
1982
)
Presence of the myelin-associated glycoprotein correlates with alterations in the periodicity of peripheral myelin.
J. Cell Biol
92
,
877
882
Uyemura
K.
,
Horie
K.
,
Kitamura
K.
,
Suzuki
M.
,
Uehara
S.
(
1979
)
Developmental changes of myelin protein in the chick peripheral nerve.
J. Neurochem
32
,
779
788
Weinberg
H. J.
,
Spencer
P. S.
(
1976
)
Studies on the control of myelinogenesis. II. Evidence for neuronal regulation of myelin production.
Brain Res
113
,
363
378
Wiktorowicz
M.
,
Roach
A.
(
1991
)
Regulation of myelin basic protein gene transcription in normal and shiverer mutant mice.
Dev. Neurosci
13
,
143
150
Wood
J. G.
,
Engel
E. L.
(
1976
)
Peripheral nerve glycoproteins and myelin fine structure during development of rat sciatic nerve.
J. Neurocytol
5
,
605
615
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