Vesicle Tethering on the Surface of Phase-Separated Active Zone Condensates.

Abstract:

:Tethering of synaptic vesicles (SVs) to the active zone determines synaptic strength, although the molecular basis governing SV tethering is elusive. Here, we discover that small unilamellar vesicles (SUVs) and SVs from rat brains coat on the surface of condensed liquid droplets formed by active zone proteins RIM, RIM-BP, and ELKS via phase separation. Remarkably, SUV-coated RIM/RIM-BP condensates are encapsulated by synapsin/SUV condensates, forming two distinct SUV pools reminiscent of the reserve and tethered SV pools that exist in presynaptic boutons. The SUV-coated RIM/RIM-BP condensates can further cluster Ca2+ channels anchored on membranes. Thus, we reconstitute a presynaptic bouton-like structure mimicking the SV-tethered active zone with its one side attached to the presynaptic membrane and the other side connected to the synapsin-clustered SV condensates. The distinct interaction modes between membraneless protein condensates and membrane-based organelles revealed here have general implications in cellular processes, including vesicular formation and trafficking, organelle biogenesis, and autophagy.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Wu X,Ganzella M,Zhou J,Zhu S,Jahn R,Zhang M

doi

10.1016/j.molcel.2020.10.029

subject

Has Abstract

pub_date

2021-01-07 00:00:00

pages

13-24.e7

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(20)30736-X

journal_volume

81

pub_type

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