Putative Cell Adhesion Membrane Protein Vstm5 Regulates Neuronal Morphology and Migration in the Central Nervous System.
During brain development, dynamic changes in neuronal membranes perform critical roles in neuronal morphogenesis and migration to create functional neural circuits. Among the proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V-set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia. Vstm5 also regulates neuronal morphology by promoting dendritic protrusions that later develop into dendritic spines. Using electroporation in utero, we found that Vstm5 overexpression delayed neuronal migration and induced multiple branches in leading processes during corticogenesis. These results indicate that Vstm5 is a new cell-adhesion-like molecule and is critically involved in synaptogenesis and corticogenesis by promoting neuronal membrane dynamics.



Neuronal migration and morphogenesis play critical roles in brain development and function. In this study, we demonstrate for the first time that V-set and transmembrane domain-containing protein 5 (Vstm5), a putative cell adhesion membrane protein, modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics. Vstm5 is also one of the target genes responsible for variations in patient responses to treatments for major depressive disorder. Our results provide the first evidence that Vstm5 is a novel factor involved in the modulation of the neuronal membrane and a critical element in normal neural circuit formation during mammalian brain development.
School of Life Sciences, National Leading Research Laboratory, and.
A-Ram
AR
Lee
School of Life Sciences, Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110.
Kwang Woo
0000-0003-3813-8913
KW
Ko
School of Life Sciences.
Hojae
H
Lee
School of Life Sciences, National Leading Research Laboratory, and GIST Research Institute (GRI), Gwangju Institute of Science and Technology (GIST), Gwangju, 500-712, Republic of Korea, and.
Yi-Seul
YS
Yoon
School of Life Sciences.
Mi-Ryoung
MR
Song
School of Life Sciences, National Leading Research Laboratory, and GIST Research Institute (GRI), Gwangju Institute of Science and Technology (GIST), Gwangju, 500-712, Republic of Korea, and cspark@gist.ac.kr.
Chul-Seung
0000-0003-0209-1412
CS
Park
D000818:Animals; D000071437:Axon Guidance / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; C000622004:V-set and transmembrane domain containing 5 protein, mouse
Vstm5; dendrite; dendritic filopodia; dendritic spine; morphogenesis; neuronal migration
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