한빛사논문, 상위피인용논문
- 조회4,117
Abstract
Kangduk Leea,1, Yoonji Kima,1, Sung-Jin Leeb, Yuan Qiangc, Dongmin Leed, Hyun Woo Leed, Hyun Kimd, H. Shawn Jec,e, Thomas C. Sudhofb,f, and Jaewon Koa,2
aDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea;
bDepartment of Molecular and Cellular Physiology and
fHoward Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305;
cProgram in Neuroscience and Behavioral Disorders, DUKE-National University of Singapore Graduate Medical School, Singapore, Republic of Singapore 169857;
dDepartment of Anatomy and Neuroscience, Korea 21 Biomedical Science, College of Medicine, Korea University, 126-1, 5-Ka, Anam-Dong, Seongbuk-Gu, Seoul 136-705, Korea; and
eDepartment of Physiology, National University of Singapore, Singapore, Republic of Singapore 117597
Contributed by Thomas C. Sudhof, November 17, 2012 (sent for review October 1, 2012)
Abstract
The MAM domain-containing GPI anchor proteins MDGA1 and MDGA2 are Ig superfamily adhesion molecules composed of six IG domains, a fibronectin III domain, a MAM domain, and a GPI anchor. MDGAs contribute to the radial migration and positioning of a subset of cortical neurons during early neural development. However, MDGAs continue to be expressed in postnatal brain, and their functions during postnatal neural development remain unknown. Here, we demonstrate that MDGAs specifically and with a nanomolar affinity bind to neuroligin-2, a cell-adhesion molecule of inhibitory synapses, but do not bind detectably to neuroligin-1 or neuroligin-3. We observed no cell adhesion between cells expressing neuroligin-2 and MDGA1, suggesting a cis interaction. Importantly, RNAi-mediated knockdown of MDGAs increased the abundance of inhibitory but not excitatory synapses in a neuroligin-2?dependent manner. Conversely, overexpression of MDGA1 decreased the numbers of functional inhibitory synapses. Likewise, coexpression of both MDGA1 and neuroligin-2 reduced the synaptogenic capacity of neuroligin-2 in an artificial synapse-formation assay by abolishing the ability of neuroligin-2 to form an adhesion complex with neurexins. Taken together, our data suggest that MDGAs inhibit the activity of neuroligin-2 in controlling the function of inhibitory synapses and that MDGAs do so by binding to neuroligin-2.
inhibitory synapse formation, synaptic cell adhesion, autism, schizophrenia
1K.L. and Y.K. contributed equally to this work.
2To whom correspondence should be addressed.
Author contributions: T.C.S. and J.K. designed research; K.L., Y.K., S.-J.L., Y.Q., D.L., H.S.J., and J.K. performed research; J.K. contributed new reagents/analytic tools; S.-J.L., Y.Q., H.W.L., H.K., H.S.J., T.C.S., and J.K. analyzed data; and H.S.J., T.C.S., and J.K. wrote the paper.
논문정보
- Research article
- 2012년 12월 (BRIC 등록일 )
- 국내(교신)+국외 연구진
- 생명과학 > 신경생물학
- 120회 이상 인용된 논문 (상위피인용논문 등록일 2023-03-10)
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