RT Journal Article
SR Electronic
T1 SorCS1-mediated Sorting of Neurexin in Dendrites Maintains Presynaptic Function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 552695
DO 10.1101/552695
A1 Luís F. Ribeiro
A1 Ben Verpoort
A1 Julie Nys
A1 Kristel M. Vennekens
A1 Keimpe D. Wierda
A1 Joris de Wit
YR 2019
UL http://biorxiv.org/content/early/2019/02/17/552695.abstract
AB The pre- and postsynaptic membranes comprising the synaptic junction differ in protein composition. The mechanisms that maintain the polarized distribution of synaptic membrane proteins are poorly understood. The sorting receptor SorCS1 is a critical trafficking regulator of neuronal receptors, including neurexin (Nrxn), a presynaptic adhesion molecule essential for synaptic transmission. We find that SorCS1 controls a balance between axonal and dendritic Nrxn1α surface levels. Newly synthesized Nrxn1α traffics to the somatodendritic surface, followed by endocytosis. SorCS1 interacts with the Rab11 effector protein Rab11FIP5/Rip11 to facilitate the transition of internalized Nrxn1α from early to recycling endosomes and bias Nrxn1α surface polarization toward the axon. In the absence of SorCS1, Nrxn1α accumulates in early endosomes and mis-polarizes to the dendritic surface, impairing presynaptic function. The axonal/dendritic balance of Nrxn1α surface distribution is activity-dependent, indicating that SorCS1-mediated sorting in somatodendritic endosomes dynamically controls Nrxn1α axonal surface polarization required for proper presynaptic function.