ELKS1 Captures Rab6-Marked Vesicular Cargo in Presynaptic Nerve Terminals.

Cell Reports
Hajnalka NyitraiPascal S Kaeser

Abstract

Neurons face unique transport challenges. They need to deliver cargo over long axonal distances and to many presynaptic nerve terminals. Rab GTPases are master regulators of vesicular traffic, but essential presynaptic Rabs have not been identified. Here, we find that Rab6, a Golgi-derived GTPase for constitutive secretion, associates with mobile axonal cargo and localizes to nerve terminals. ELKS1 is a stationary presynaptic protein with Golgin homology that binds to Rab6. Knockout and rescue experiments for ELKS1 and Rab6 establish that ELKS1 captures Rab6 cargo. The ELKS1-Rab6-capturing mechanism can be transferred to mitochondria by mistargeting ELKS1 or Rab6 to them. We conclude that nerve terminals have repurposed mechanisms from constitutive exocytosis for their highly regulated secretion. By employing Golgin-like mechanisms with anchored ELKS extending its coiled-coils to capture Rab6 cargo, they have spatially separated cargo capture from fusion. ELKS complexes connect to active zones and may mediate vesicle progression toward release sites.

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Citations

Nov 18, 2020·Molecular Cell·Xiandeng WuMingjie Zhang
May 13, 2021·Current Opinion in Neurobiology·Nathan A McDonald, Kang Shen
May 26, 2021·Nature Communications·Javier Emperador-MeleroPascal S Kaeser

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Methods Mentioned

BETA
GTPases
confocal microscopy
super-resolution microscopy
transmission electron microscopy
affinity purifications
affinity purification
electron microscopy
fluorescence microscopy
GTPase
transfection

Key Resources (RRID) Mentioned

MMRRC_049340
MMRRC_041523
IMSR_
IMSR_JAX

Software Mentioned

GraphPad Prism
MATLAB
SynapseEM
ImageJ

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