Glutamate Signaling and Neuroligin/Neurexin Adhesion Play Opposing Roles That Are Mediated by Major Histocompatibility Complex I Molecules in Cortical Synapse Formation.

Autor:	Sell GL; Center for Neuroscience, University of California, Davis, Davis, California 95618., Barrow SL; Center for Neuroscience, University of California, Davis, Davis, California 95618., McAllister AK; Center for Neuroscience, University of California, Davis, Davis, California 95618 mcallik@wfu.edu.; Department of Biology, Wake Forest University, Winston-Salem, North Carolina 27109.; Department of Translational Neuroscience, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2024 Dec 04; Vol. 44 (49). Date of Electronic Publication: 2024 Dec 04.
DOI:	10.1523/JNEUROSCI.0797-24.2024
Abstrakt:	Although neurons release neurotransmitter before contact, the role for this release in synapse formation remains unclear. Cortical synapses do not require synaptic vesicle release for formation (Verhage et al., 2000; Sando et al., 2017; Sigler et al., 2017; Held et al., 2020), yet glutamate clearly regulates glutamate receptor trafficking (Roche et al., 2001; Nong et al., 2004) and induces spine formation (Engert and Bonhoeffer, 1999; Maletic-Savatic et al., 1999; Toni et al., 1999; Kwon and Sabatini, 2011; Oh et al., 2016). Using rat and murine culture systems to dissect molecular mechanisms, we found that glutamate rapidly decreases synapse density specifically in young cortical neurons in a local and calcium-dependent manner through decreasing N -methyl-d-aspartate receptor (NMDAR) transport and surface expression as well as cotransport with neuroligin (NL1). Adhesion between NL1 and neurexin 1 protects against this glutamate-induced synapse loss. Major histocompatibility I (MHCI) molecules are required for the effects of glutamate in causing synapse loss through negatively regulating NL1 levels in both sexes. Thus, like acetylcholine at the neuromuscular junction, glutamate acts as a dispersal signal for NMDARs and causes rapid synapse loss unless opposed by NL1-mediated trans-synaptic adhesion. Together, glutamate, MHCI, and NL1 mediate a novel form of homeostatic plasticity in young neurons that induces rapid changes in NMDARs to regulate when and where nascent glutamatergic synapses are formed. Competing Interests: The authors declare no competing financial interests. (Copyright © 2024 the authors.)
Databáze:	MEDLINE
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