M6a is expressed in the murine neural retina and regulates neurite extension.
OBJECTIVE
Glycoprotein m6a (M6a) is a cell-surface glycoprotein that belongs to the myelin proteolipid protein family. M6a is expressed mainly in the nervous system, and its expression and function in mammalian retina have not been described. Using proteomics analysis of mouse retinal membrane fractions, we identified M6a as a retinal membrane protein that is strongly expressed at embryonic stages. Our aim was to reveal the function of M6a in development of mouse retina in this work.


METHODS
Detailed expression pattern of M6a was examined by immunostaining using frozen sections of mouse retina obtained at various developmental stages. For functional analysis of M6a in mouse retinal development, we performed retorovirus-mediated overexpression of M6a in mouse retinal explant culture. Then, cell differentiation, proliferation and structural maturation of the cells were examined.


RESULTS
M6a transcripts were strongly expressed in embryonic retina. After completion of retinal differentiation, the level of expression decreased as mouse development progressed. Immunohistochemistry showed that in the immature mouse retina, M6a was strongly expressed in the axons of retinal ganglion cells. After birth, M6a expression was confined to the inner plexiform layer, and finally, to the inner and outer plexiform layers of adult mouse retina. M6a expression was completely paralleled by that of the synaptic marker, synaptophysin. Mouse retinal progenitor cells that overexpressed M6a following retrovirus-mediated gene transfer were subjected to in vitro explant or monolayer cultures. The neurite outgrowth of M6a-overexpressing retinal cells was strikingly enhanced, although M6a did not affect differentiation and proliferation.


CONCLUSIONS
These results suggest that M6a plays a role in retinal development by regulating neurites, and it may also function to modulate synaptic activities in the adult retina.
Zhao
Jing
J
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Iida
Atsumi
A
Ouchi
Yasuo
Y
Satoh
Shinya
S
Watanabe
Sumiko
S
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D021381:Protein Transport; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D015415:Biomarkers; C083480:Gpm6a protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins
Biochem J. 2007 Nov 15;408(1):51-9
17688421
Trends Neurosci. 2002 Jan;25(1):32-8
11801336
Biochem Biophys Res Commun. 2002 Oct 4;297(4):722-8
12359212
J Neurocytol. 1998 Sep;27(9):695-703
10447243
Gene Ther. 2000 Jun;7(12):1063-6
10871756
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17196-201
16286650
Mol Cell Biol. 2004 May;24(10):4513-21
15121868
J Cell Sci. 2005 Oct 1;118(Pt 19):4473-83
16179606
J Neurobiol. 1992 Feb;23(1):71-88
1564456
J Comp Neurol. 1996 Jul 08;370(4):465-78
8807448
J Neurosci. 1991 Jun;11(6):1617-26
1904480
J Neurosci Res. 1999 Jul 1;57(1):13-22
10397631
Neuron. 1993 Sep;11(3):423-31
8398137
Mech Dev. 1998 Aug;76(1-2):3-18
9767078
Dev Dyn. 1992 Aug;194(4):311-25
1286213
Brain Res Dev Brain Res. 2003 Oct 10;145(1):93-105
14519497
Nature. 2000 Jan 6;403(6765):93-8
10638760
Dev Biol. 2006 Apr 1;292(1):265-76
16499901
Dev Biol. 2007 Jan 1;301(1):141-54
17069792
J Neurosci. 2002 Sep 1;22(17):7398-407
12196561
Neuron. 1994 Mar;12(3):583-95
7512350
Int J Cancer. 1983 Jan 15;31(1):13-20
6339421