본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Proceedings of the National Academy of Sciences of the United States of America v.114 no.4, 2017년, pp.E610 - E618   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation

Thakar, Sonal (Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093 ) ; Wang, Liqing (Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093 ) ; Yu, Ting (Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093 ) ; Ye, Mao (Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093 ) ; Onishi, Keisuke (Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093 ) ; Scott, John (Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093 ) ; Qi, Jiaxuan (Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093 ) ; Fernandes, Catarina (Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093 ) ; Han, Xuemei (Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037 ) ; Yates III, John R. (Department of Chemical P ) ; Berg, Darwin K. ; Zou, Yimin ;
  • 초록  

    Significance The signaling mechanisms mediating glutamatergic synapse assembly are fundamental to our understanding of neural circuit function, plasticity, and disorders, but have remained elusive. We provide direct evidence that two components of the conserved planar cell polarity signaling pathway, which assembles asymmetric cell–cell junctions, have opposing functions in glutamatergic synapse formation. Celsr3 promotes assembly whereas Vangl2 inhibits assembly, suggesting that this signaling mechanism is accessible for both positive and negative regulation and is also a candidate pathway for mediating synaptic plasticity. The signaling mechanisms that choreograph the assembly of the highly asymmetric pre- and postsynaptic structures are still poorly defined. Using synaptosome fractionation, immunostaining, and coimmunoprecipitation, we found that Celsr3 and Vangl2, core components of the planar cell polarity (PCP) pathway, are localized at developing glutamatergic synapses and interact with key synaptic proteins. Pyramidal neurons from the hippocampus of Celsr3 knockout mice exhibit loss of ∼50% of glutamatergic synapses, but not inhibitory synapses, in culture. Wnts are known regulators of synapse formation, and our data reveal that Wnt5a inhibits glutamatergic synapses formed via Celsr3. To avoid affecting earlier developmental processes, such as axon guidance, we conditionally knocked out Celsr3 in the hippocampus 1 week after birth. The CA1 neurons that lost Celsr3 also showed a loss of ∼50% of glutamatergic synapses in vivo without affecting the inhibitory synapses assessed by miniature excitatory postsynaptic current (mEPSC) and electron microscopy. These animals displayed deficits in hippocampus-dependent behaviors in adulthood, including spatial learning and memory and fear conditioning. In contrast to Celsr3 conditional knockouts, we found that the conditional knockout of Vangl2 in the hippocampus 1 week after birth led to a large increase in synaptic density, as evaluated by mEPSC frequency and spine density. PCP signaling is mediated by multiple core components with antagonizing functions. Our results document the opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation.


  • 주제어

    Celsr3 .   Vangl2 .   glutamatergic .   synapse formation.  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기