The interconnected roles of spastin and protrudin in endosomal sorting
type: CreativeWork
description: Endosomal tubule fission is associated with endoplasmic reticulum (ER)-endosome membrane contact sites and several ER proteins are required for efficient endosomal tubule fission. Our lab has previously identified two hereditary spastic paraplegia (HSP)- associated proteins, spastin (SPG4) and atlastin-1 (SPG3A), as essential for endosomal tubule fission. I investigated the functional interaction of spastin and protrudin and found that protrudin, an ER-associated adaptor molecule involved in anterograde membrane traffic, is a novel factor regulating endosomal tubule fission in non-polarised cells and in human iPSC-derived neurons. This required protrudin’s ability to bind VAPA/B and endosomal PtdIns3P, as well as its coiled coil domain previously implicated in kinesin-1 interaction. Tug-of-war between kinesin and dynein microtubule motors has been shown to be essential for endosomal tubule fission and I propose that protrudin functions in this process by promoting endosome interactions with kinesin-1, which generates anterograde pulling force on the endosome to counter-balance retrograde pulling force generated by dyneins. This work expands the repertoire of ER proteins involved in endosomal tubule fission and helps to understand how microtubule motors interact with other organelles to regulate membrane trafficking events. Considering protrudin is a potent enhancer of axon regeneration in the central nervous system, this might also help to elucidate the mechanisms underlying axonal health.
abstract: Endosomal tubule fission is associated with endoplasmic reticulum (ER)-endosome membrane contact sites and several ER proteins are required for efficient endosomal tubule fission. Our lab has previously identified two hereditary spastic paraplegia (HSP)- associated proteins, spastin (SPG4) and atlastin-1 (SPG3A), as essential for endosomal tubule fission. I investigated the functional interaction of spastin and protrudin and found that protrudin, an ER-associated adaptor molecule involved in anterograde membrane traffic, is a novel factor regulating endosomal tubule fission in non-polarised cells and in human iPSC-derived neurons. This required protrudin’s ability to bind VAPA/B and endosomal PtdIns3P, as well as its coiled coil domain previously implicated in kinesin-1 interaction. Tug-of-war between kinesin and dynein microtubule motors has been shown to be essential for endosomal tubule fission and I propose that protrudin functions in this process by promoting endosome interactions with kinesin-1, which generates anterograde pulling force on the endosome to counter-balance retrograde pulling force generated by dyneins. This work expands the repertoire of ER proteins involved in endosomal tubule fission and helps to understand how microtubule motors interact with other organelles to regulate membrane trafficking events. Considering protrudin is a potent enhancer of axon regeneration in the central nervous system, this might also help to elucidate the mechanisms underlying axonal health.
author: Kleniuk, Julia
language: eng
keywords: endosome, neuron, hereditary spastic paraplegia, protrudin, spastin
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/3040af0f-b991-4264-ac93-01542d8adf05/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2024-06-03
date modified: 2026-07-22T22:24:00Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.113678