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CRMP 1 and CRMP 2 have synergistic but distinct roles in dendritic development
Author(s) -
Makihara Hiroko,
Nakai Shiori,
Ohkubo Wataru,
Yamashita Naoya,
Nakamura Fumio,
Kiyonari Hiroshi,
Shioi Go,
JitsukiTakahashi Aoi,
Nakamura Haruko,
Tanaka Fumiaki,
Akase Tomoko,
Kolattukudy Pappachan,
Goshima Yoshio
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12399
Subject(s) - semaphorin , biology , sema3a , dendritic spine , mediator , neuroscience , microbiology and biotechnology , plexin , receptor , genetics , hippocampal formation
Collapsin response mediator protein 2, CRMP 2, has been identified as an intracellular signaling mediator for Semaphorin 3A (Sema3A). CRMP 2 plays a key role in axon guidance, dendritic morphogenesis, and cell polarization. It has been also implicated in a variety of neurological and psychiatric disorders. However, the in vivo functions of CRMP 2 remain unknown. We generated CRMP 2 gene‐deficient ( crmp2 −/− ) mice. The crmp2 −/− mice showed irregular development of dendritic spines in cortical neurons. The density of dendritic spines was reduced in the cortical layer V pyramidal neurons of crmp2 −/− mice as well as in those of sema3A −/− and crmp1 −/− mice. However, no abnormality was found in dendritic patterning in crmp2 −/− compared to wild‐type ( WT ) neurons. The level of CRMP 1 was increased in crmp2 −/− , but the level of CRMP 2 was not altered in crmp1 −/− compared to WT cortical brain lysates. Dendritic spine density and branching were reduced in double‐heterozygous sema3A +/− ; crmp2 +/− and sema3A +/− ; crmp1 +/− mice. The phenotypic defects had no genetic interaction between crmp1 and crmp2 . These findings suggest that both CRMP 1 and CRMP 2 mediate Sema3A signaling to regulate dendritic spine maturation and patterning, but through overlapping and distinct signaling pathways.