title: mSYD1A, a mammalian synapse-defective-1 protein, regulates synaptogenic signaling and vesicle docking.
abstract: Structure and function of presynaptic terminals are critical for the transmission and processing of neuronal signals. Trans-synaptic signaling systems instruct the differentiation and function of presynaptic release sites, but their downstream mediators are only beginning to be understood. Here, we identify the intracellular mSYD1A (mouse Synapse-Defective-1A) as a regulator of presynaptic function in mice. mSYD1A forms a complex with presynaptic receptor tyrosine phosphatases and controls tethering of synaptic vesicles at synapses. mSYD1A function relies on an intrinsically disordered domain that interacts with multiple structurally unrelated binding partners, including the active zone protein liprin-α2 and nsec1/munc18-1. In mSYD1A knockout mice, synapses assemble in normal numbers but there is a significant reduction in synaptic vesicle docking at the active zone and an impairment of synaptic transmission. Thus, mSYD1A is a regulator of presynaptic release sites at central synapses.
authors.affiliation: Biozentrum, University of Basel, 4056 Basel, Switzerland.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wentzel
authors.forename: Julia E
authors.initials: JE
authors.lastname: Sommer
authors.forename: Ramya
authors.initials: R
authors.lastname: Nair
authors.forename: Adeline
authors.initials: A
authors.lastname: Stiefvater
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Sibarita
authors.forename: Peter
authors.initials: P
authors.lastname: Scheiffele
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; C583137:synapse-defective-1A protein, mouse; D020741:rho GTP-Binding Proteins