Tags

Type your tag names separated by a space and hit enter

SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function.
PLoS Biol. 2019 10; 17(10):e3000466.PB

Abstract

The pre- and postsynaptic membranes comprising the synaptic junction differ in protein composition. The membrane trafficking mechanisms by which neurons control surface polarization of synaptic receptors remain poorly understood. The sorting receptor Sortilin-related CNS expressed 1 (SorCS1) is a critical regulator of trafficking of neuronal receptors, including the presynaptic adhesion molecule neurexin (Nrxn), an essential synaptic organizer. Here, we show that SorCS1 maintains a balance between axonal and dendritic Nrxn surface levels in the same neuron. Newly synthesized Nrxn1α traffics to the dendritic surface, where it is endocytosed. Endosomal SorCS1 interacts with the Rab11 GTPase effector Rab11 family-interacting protein 5 (Rab11FIP5)/Rab11 interacting protein (Rip11) to facilitate the transition of internalized Nrxn1α from early to recycling endosomes and bias Nrxn1α surface polarization towards the axon. In the absence of SorCS1, Nrxn1α accumulates in early endosomes and mispolarizes to the dendritic surface, impairing presynaptic differentiation and function. Thus, SorCS1-mediated sorting in dendritic endosomes controls Nrxn axonal surface polarization required for proper synapse development and function.

Authors+Show Affiliations

VIB Center for Brain & Disease Research, Herestraat, Leuven, Belgium. KU Leuven, Department of Neurosciences, Leuven Brain Institute, Herestraat, Leuven, Belgium.VIB Center for Brain & Disease Research, Herestraat, Leuven, Belgium. KU Leuven, Department of Neurosciences, Leuven Brain Institute, Herestraat, Leuven, Belgium.VIB Center for Brain & Disease Research, Herestraat, Leuven, Belgium. KU Leuven, Department of Neurosciences, Leuven Brain Institute, Herestraat, Leuven, Belgium.VIB Center for Brain & Disease Research, Herestraat, Leuven, Belgium. KU Leuven, Department of Neurosciences, Leuven Brain Institute, Herestraat, Leuven, Belgium.VIB Center for Brain & Disease Research, Herestraat, Leuven, Belgium. KU Leuven, Department of Neurosciences, Leuven Brain Institute, Herestraat, Leuven, Belgium.VIB Center for Brain & Disease Research, Herestraat, Leuven, Belgium. KU Leuven, Department of Neurosciences, Leuven Brain Institute, Herestraat, Leuven, Belgium.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31658245

Citation

Ribeiro, Luís F., et al. "SorCS1-mediated Sorting in Dendrites Maintains Neurexin Axonal Surface Polarization Required for Synaptic Function." PLoS Biology, vol. 17, no. 10, 2019, pp. e3000466.
Ribeiro LF, Verpoort B, Nys J, et al. SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function. PLoS Biol. 2019;17(10):e3000466.
Ribeiro, L. F., Verpoort, B., Nys, J., Vennekens, K. M., Wierda, K. D., & de Wit, J. (2019). SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function. PLoS Biology, 17(10), e3000466. https://doi.org/10.1371/journal.pbio.3000466
Ribeiro LF, et al. SorCS1-mediated Sorting in Dendrites Maintains Neurexin Axonal Surface Polarization Required for Synaptic Function. PLoS Biol. 2019;17(10):e3000466. PubMed PMID: 31658245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function. AU - Ribeiro,Luís F, AU - Verpoort,Ben, AU - Nys,Julie, AU - Vennekens,Kristel M, AU - Wierda,Keimpe D, AU - de Wit,Joris, Y1 - 2019/10/28/ PY - 2019/07/02/received PY - 2019/10/08/accepted PY - 2019/11/07/revised PY - 2019/10/29/pubmed PY - 2020/2/28/medline PY - 2019/10/29/entrez SP - e3000466 EP - e3000466 JF - PLoS biology JO - PLoS Biol. VL - 17 IS - 10 N2 - The pre- and postsynaptic membranes comprising the synaptic junction differ in protein composition. The membrane trafficking mechanisms by which neurons control surface polarization of synaptic receptors remain poorly understood. The sorting receptor Sortilin-related CNS expressed 1 (SorCS1) is a critical regulator of trafficking of neuronal receptors, including the presynaptic adhesion molecule neurexin (Nrxn), an essential synaptic organizer. Here, we show that SorCS1 maintains a balance between axonal and dendritic Nrxn surface levels in the same neuron. Newly synthesized Nrxn1α traffics to the dendritic surface, where it is endocytosed. Endosomal SorCS1 interacts with the Rab11 GTPase effector Rab11 family-interacting protein 5 (Rab11FIP5)/Rab11 interacting protein (Rip11) to facilitate the transition of internalized Nrxn1α from early to recycling endosomes and bias Nrxn1α surface polarization towards the axon. In the absence of SorCS1, Nrxn1α accumulates in early endosomes and mispolarizes to the dendritic surface, impairing presynaptic differentiation and function. Thus, SorCS1-mediated sorting in dendritic endosomes controls Nrxn axonal surface polarization required for proper synapse development and function. SN - 1545-7885 UR - https://www.unboundmedicine.com/medline/citation/31658245/SorCS1_mediated_sorting_in_dendrites_maintains_neurexin_axonal_surface_polarization_required_for_synaptic_function_ L2 - http://dx.plos.org/10.1371/journal.pbio.3000466 DB - PRIME DP - Unbound Medicine ER -