51. Transsynaptic Binding of Orphan Receptor GPR179 to Dystroglycan-Pikachurin Complex Is Essential for the Synaptic Organization of Photoreceptors
- Author
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Joris de Wit, Yoshihiro Omori, Cesare Orlandi, Yan Cao, Akiko Ueno, Michel Roux, Yuchen Wang, Takahisa Furukawa, Giuseppe Condomitti, Motoi Kanagawa, Kirill A. Martemyanov, Scripps Research Institute, Institute for Protein Research [Osaka], Osaka University [Osaka], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Division of Molecular Brain Science, and Kobe University
- Subjects
0301 basic medicine ,Nervous system ,synaptic specificity ,retina ,orphan receptor ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,heparan sulfate proteoglycan ,HEPARAN-SULFATE PROTEOGLYCANS ,Ribbon synapse ,Receptors, G-Protein-Coupled ,Mice ,0302 clinical medicine ,LIGHT RESPONSE ,Dystroglycans ,lcsh:QH301-705.5 ,GENE-EXPRESSION ,Mice, Knockout ,Orphan receptor ,biology ,Chemistry ,Cell adhesion molecule ,STATIONARY NIGHT BLINDNESS ,Extracellular Matrix ,3. Good health ,Cell biology ,medicine.anatomical_structure ,ON-bipolar cells ,HSPG ,Life Sciences & Biomedicine ,Protein Binding ,ON-BIPOLAR NEURONS ,GROWTH-FACTOR ,vision ,Nerve Tissue Proteins ,Neurotransmission ,Article ,General Biochemistry, Genetics and Molecular Biology ,DUCHENNE MUSCULAR-DYSTROPHY ,03 medical and health sciences ,PROTEIN-COUPLED RECEPTORS ,Glycoprotein complex ,Dystroglycan ,medicine ,Animals ,Humans ,synaptic transmission ,Photoreceptor Cells ,ribbon synapse ,Science & Technology ,Cell Biology ,IN-VITRO ,transsynaptic interactions ,carbohydrates (lipids) ,HEK293 Cells ,030104 developmental biology ,lcsh:Biology (General) ,Synapses ,biology.protein ,Pikachurin ,SIGNALING CASCADE ,sense organs ,Carrier Proteins ,030217 neurology & neurosurgery - Abstract
SUMMARY Establishing synaptic contacts between neurons is paramount for nervous system function. This process involves transsynaptic interactions between a host of cell adhesion molecules that act in cooperation with the proteins of the extracellular matrix to specify uniquephysiological propertiesofindividual synaptic connections. However, understanding of the molecular mechanisms that generate functional diversity in an input-specific fashion is limited. In this study, we identify that major components of the extracellular matrix proteins present in the synaptic cleft—members oftheheparansulfateproteoglycan (HSPG) family—associate with the GPR158/179 group of orphan receptors. Using the mammalian retina as a model system, we demonstrate that the HSPG member Pikachurin, released by photoreceptors, recruits a key post-synaptic signaling complex of downstream ON-bipolar neurons in coordination with the presynaptic dystroglycan glycoprotein complex. We further demonstrate that this transsynaptic assembly plays an essential role in synaptic transmission of photoreceptor signals., Graphical Abstract, In Brief Orlandi et al. identify transsynaptic assembly at photoreceptor synapses involving pre-synaptic dystrophindystroglycan complex and the postsynaptic orphan receptor GPR179 bridged by HSPG protein Pikachurin in the cleft and demonstrate its role in shaping transmission of photoreceptor signals.
- Published
- 2018