EHD3 regulates early-endosome-to-Golgi transport and preserves Golgi morphology

Naava Naslavsky, Jenna McKenzie, Nihal Altan-Bonnet, David Sheff, Steven H Caplan

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Depletion of EHD3 affects sorting in endosomes by altering the kinetics and route of receptor recycling to the plasma membrane. Here we demonstrate that siRNA knockdown of EHD3, or its interaction partner rabenosyn-5, causes redistribution of sorting nexin 1 (SNX1) to enlarged early endosomes and disrupts transport of internalized Shiga toxin B subunit (STxB) to the Golgi. Moreover, under these conditions, Golgi morphology appears as a series of highly dispersed and fragmented stacks that maintain characteristics of cis-, medial-and trans-Golgi membranes. Although Arf1 still assembled onto these dispersed Golgi membranes, the level of AP-1 γ-adaptin recruited to the Golgi was diminished. Whereas VSV-G-secretion from the dispersed Golgi remained largely unaffected, the distribution of mannose 6-phosphate receptor (M6PR) was altered: it remained in peripheral endosomes and did not return to the Golgi. Cathepsin D, a hydrolase that is normally transported to lysosomes via an M6PR-dependent pathway, remained trapped at the Golgi. Our findings support a role for EHD3 in regulating endosome-to-Golgi transport, and as a consequence, lysosomal biosynthetic, but not secretory, transport pathways are also affected. These data also suggest that impaired endosome-to-Golgi transport and the resulting lack of recruitment of AP-1 γ-adaptin to Golgi membranes affect Golgi morphology.

Original languageEnglish (US)
Pages (from-to)389-400
Number of pages12
JournalJournal of Cell Science
Volume122
Issue number3
DOIs
StatePublished - Feb 1 2009

Fingerprint

Endosomes
IGF Type 2 Receptor
Transcription Factor AP-1
Membranes
Sorting Nexins
Shiga Toxin
Cathepsin D
Secretory Pathway
Hydrolases
Lysosomes
Small Interfering RNA
Cell Membrane

Keywords

  • EHD3
  • Early endosome
  • Golgi
  • Mannose-6-phosphate receptor
  • Retrograde transport

ASJC Scopus subject areas

  • Cell Biology

Cite this

EHD3 regulates early-endosome-to-Golgi transport and preserves Golgi morphology. / Naslavsky, Naava; McKenzie, Jenna; Altan-Bonnet, Nihal; Sheff, David; Caplan, Steven H.

In: Journal of Cell Science, Vol. 122, No. 3, 01.02.2009, p. 389-400.

Research output: Contribution to journalArticle

Naslavsky, Naava ; McKenzie, Jenna ; Altan-Bonnet, Nihal ; Sheff, David ; Caplan, Steven H. / EHD3 regulates early-endosome-to-Golgi transport and preserves Golgi morphology. In: Journal of Cell Science. 2009 ; Vol. 122, No. 3. pp. 389-400.
@article{17298cf0a27841978142dcd50bc56979,
title = "EHD3 regulates early-endosome-to-Golgi transport and preserves Golgi morphology",
abstract = "Depletion of EHD3 affects sorting in endosomes by altering the kinetics and route of receptor recycling to the plasma membrane. Here we demonstrate that siRNA knockdown of EHD3, or its interaction partner rabenosyn-5, causes redistribution of sorting nexin 1 (SNX1) to enlarged early endosomes and disrupts transport of internalized Shiga toxin B subunit (STxB) to the Golgi. Moreover, under these conditions, Golgi morphology appears as a series of highly dispersed and fragmented stacks that maintain characteristics of cis-, medial-and trans-Golgi membranes. Although Arf1 still assembled onto these dispersed Golgi membranes, the level of AP-1 γ-adaptin recruited to the Golgi was diminished. Whereas VSV-G-secretion from the dispersed Golgi remained largely unaffected, the distribution of mannose 6-phosphate receptor (M6PR) was altered: it remained in peripheral endosomes and did not return to the Golgi. Cathepsin D, a hydrolase that is normally transported to lysosomes via an M6PR-dependent pathway, remained trapped at the Golgi. Our findings support a role for EHD3 in regulating endosome-to-Golgi transport, and as a consequence, lysosomal biosynthetic, but not secretory, transport pathways are also affected. These data also suggest that impaired endosome-to-Golgi transport and the resulting lack of recruitment of AP-1 γ-adaptin to Golgi membranes affect Golgi morphology.",
keywords = "EHD3, Early endosome, Golgi, Mannose-6-phosphate receptor, Retrograde transport",
author = "Naava Naslavsky and Jenna McKenzie and Nihal Altan-Bonnet and David Sheff and Caplan, {Steven H}",
year = "2009",
month = "2",
day = "1",
doi = "10.1242/jcs.037051",
language = "English (US)",
volume = "122",
pages = "389--400",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "3",

}

TY - JOUR

T1 - EHD3 regulates early-endosome-to-Golgi transport and preserves Golgi morphology

AU - Naslavsky, Naava

AU - McKenzie, Jenna

AU - Altan-Bonnet, Nihal

AU - Sheff, David

AU - Caplan, Steven H

PY - 2009/2/1

Y1 - 2009/2/1

N2 - Depletion of EHD3 affects sorting in endosomes by altering the kinetics and route of receptor recycling to the plasma membrane. Here we demonstrate that siRNA knockdown of EHD3, or its interaction partner rabenosyn-5, causes redistribution of sorting nexin 1 (SNX1) to enlarged early endosomes and disrupts transport of internalized Shiga toxin B subunit (STxB) to the Golgi. Moreover, under these conditions, Golgi morphology appears as a series of highly dispersed and fragmented stacks that maintain characteristics of cis-, medial-and trans-Golgi membranes. Although Arf1 still assembled onto these dispersed Golgi membranes, the level of AP-1 γ-adaptin recruited to the Golgi was diminished. Whereas VSV-G-secretion from the dispersed Golgi remained largely unaffected, the distribution of mannose 6-phosphate receptor (M6PR) was altered: it remained in peripheral endosomes and did not return to the Golgi. Cathepsin D, a hydrolase that is normally transported to lysosomes via an M6PR-dependent pathway, remained trapped at the Golgi. Our findings support a role for EHD3 in regulating endosome-to-Golgi transport, and as a consequence, lysosomal biosynthetic, but not secretory, transport pathways are also affected. These data also suggest that impaired endosome-to-Golgi transport and the resulting lack of recruitment of AP-1 γ-adaptin to Golgi membranes affect Golgi morphology.

AB - Depletion of EHD3 affects sorting in endosomes by altering the kinetics and route of receptor recycling to the plasma membrane. Here we demonstrate that siRNA knockdown of EHD3, or its interaction partner rabenosyn-5, causes redistribution of sorting nexin 1 (SNX1) to enlarged early endosomes and disrupts transport of internalized Shiga toxin B subunit (STxB) to the Golgi. Moreover, under these conditions, Golgi morphology appears as a series of highly dispersed and fragmented stacks that maintain characteristics of cis-, medial-and trans-Golgi membranes. Although Arf1 still assembled onto these dispersed Golgi membranes, the level of AP-1 γ-adaptin recruited to the Golgi was diminished. Whereas VSV-G-secretion from the dispersed Golgi remained largely unaffected, the distribution of mannose 6-phosphate receptor (M6PR) was altered: it remained in peripheral endosomes and did not return to the Golgi. Cathepsin D, a hydrolase that is normally transported to lysosomes via an M6PR-dependent pathway, remained trapped at the Golgi. Our findings support a role for EHD3 in regulating endosome-to-Golgi transport, and as a consequence, lysosomal biosynthetic, but not secretory, transport pathways are also affected. These data also suggest that impaired endosome-to-Golgi transport and the resulting lack of recruitment of AP-1 γ-adaptin to Golgi membranes affect Golgi morphology.

KW - EHD3

KW - Early endosome

KW - Golgi

KW - Mannose-6-phosphate receptor

KW - Retrograde transport

UR - http://www.scopus.com/inward/record.url?scp=65249113299&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65249113299&partnerID=8YFLogxK

U2 - 10.1242/jcs.037051

DO - 10.1242/jcs.037051

M3 - Article

VL - 122

SP - 389

EP - 400

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 3

ER -