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Isoform-specific cleavage of neuroligin-3 reduces synapse strength.
Bemben, Michael A; Nguyen, Thien A; Li, Yan; Wang, Tongguang; Nicoll, Roger A; Roche, Katherine W.
Afiliación
  • Bemben MA; Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, 20892, USA. michael.bemben@ucsf.edu.
  • Nguyen TA; Departments of Cellular and Molecular Pharmacology and Physiology, University of California, San Francisco, San Francisco, CA, 94158, USA. michael.bemben@ucsf.edu.
  • Li Y; Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, 20892, USA.
  • Wang T; Department of Pharmacology and Physiology, Georgetown University, Washington D.C., WA, 20057, USA.
  • Nicoll RA; Protein/Peptide Sequencing Facility, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, 20892, USA.
  • Roche KW; Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, 20892, USA.
Mol Psychiatry ; 24(1): 145-160, 2019 01.
Article en En | MEDLINE | ID: mdl-30242227
The assembly and maintenance of synapses are dynamic processes that require bidirectional contacts between the pre- and postsynaptic structures. A network of adhesion molecules mediate this physical interaction between neurons. How synapses are disassembled and if there are distinct mechanisms that govern the removal of specific adhesion molecules remain unclear. Here, we report isoform-specific proteolytic cleavage of neuroligin-3 in response to synaptic activity and protein kinase C signaling resulting in reduced synapse strength. Although neuroligin-1 and neuroligin-2 are not directly cleaved by this pathway, when heterodimerized with neuroligin-3, they too undergo proteolytic cleavage. Thus protein kinase C-dependent cleavage is mediated through neuroligin-3. Recent studies on glioma implicate the neuroligin-3 ectodomain as a mitogen. Here we demonstrate: (1) there are mechanisms governing specific adhesion molecule remodeling; (2) neuroligin-3 is a key regulator of neuroligin cleavage events; and (3) there are two cleavage pathways; basal and activity-dependent that produce the mitogenic form of neuroligin-3.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Moléculas de Adhesión Celular Neuronal / Proteínas de la Membrana / Proteínas del Tejido Nervioso Límite: Animals / Female / Humans / Male Idioma: En Revista: Mol Psychiatry Asunto de la revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Moléculas de Adhesión Celular Neuronal / Proteínas de la Membrana / Proteínas del Tejido Nervioso Límite: Animals / Female / Humans / Male Idioma: En Revista: Mol Psychiatry Asunto de la revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido