Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis

Sai Srinivas Panapakkam Giridharan, Bishuang Cai, Nicolas Vitale, Naava Naslavsky, Steven H Caplan

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Endocytic transport necessitates the generation of membrane tubules and their subsequent fission to transport vesicles for sorting of cargo molecules. The endocytic recycling compartment, an array of tubular and vesicular membranes decorated by the Eps15 homology domain protein, EHD1, is responsible for receptor and lipid recycling to the plasma membrane. It has been proposed that EHD dimers bind and bend membranes, thus generating recycling endosome (RE) tubules. However, recent studies show that molecules interacting with CasL-Like1 (MICAL-L1), a second, recently identified RE tubule marker, recruits EHD1 to preexisting tubules. The mechanisms and events supporting the generation of tubular recycling endosomes were unclear. Here, we propose a mechanism for the biogenesis of RE tubules. We demonstrate that MICAL-L1 and the BAR-domain protein syndapin2 bind to phosphatidic acid, which we identify as a novel lipid component of RE. Our studies demonstrate that direct interactions between these two proteins stabilize their association with membranes, allowing for nucleation of tubules by syndapin2. Indeed, the presence of phosphatidic acid in liposomes enhances the ability of syndapin2 to tubulate membranes in vitro. Overall our results highlight a new role for phosphatidic acid in endocytic recycling and provide new insights into the mechanisms by which tubular REs are generated.

Original languageEnglish (US)
Pages (from-to)1776-1790
Number of pages15
JournalMolecular biology of the cell
Volume24
Issue number11
DOIs
StatePublished - Jun 1 2013

Fingerprint

Phosphatidic Acids
Endosomes
Membranes
Lipids
Transport Vesicles
Recycling
Liposomes
Cell Membrane
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis. / Giridharan, Sai Srinivas Panapakkam; Cai, Bishuang; Vitale, Nicolas; Naslavsky, Naava; Caplan, Steven H.

In: Molecular biology of the cell, Vol. 24, No. 11, 01.06.2013, p. 1776-1790.

Research output: Contribution to journalArticle

Giridharan, Sai Srinivas Panapakkam ; Cai, Bishuang ; Vitale, Nicolas ; Naslavsky, Naava ; Caplan, Steven H. / Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis. In: Molecular biology of the cell. 2013 ; Vol. 24, No. 11. pp. 1776-1790.
@article{2df20c34670e450995f379d081b7defe,
title = "Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis",
abstract = "Endocytic transport necessitates the generation of membrane tubules and their subsequent fission to transport vesicles for sorting of cargo molecules. The endocytic recycling compartment, an array of tubular and vesicular membranes decorated by the Eps15 homology domain protein, EHD1, is responsible for receptor and lipid recycling to the plasma membrane. It has been proposed that EHD dimers bind and bend membranes, thus generating recycling endosome (RE) tubules. However, recent studies show that molecules interacting with CasL-Like1 (MICAL-L1), a second, recently identified RE tubule marker, recruits EHD1 to preexisting tubules. The mechanisms and events supporting the generation of tubular recycling endosomes were unclear. Here, we propose a mechanism for the biogenesis of RE tubules. We demonstrate that MICAL-L1 and the BAR-domain protein syndapin2 bind to phosphatidic acid, which we identify as a novel lipid component of RE. Our studies demonstrate that direct interactions between these two proteins stabilize their association with membranes, allowing for nucleation of tubules by syndapin2. Indeed, the presence of phosphatidic acid in liposomes enhances the ability of syndapin2 to tubulate membranes in vitro. Overall our results highlight a new role for phosphatidic acid in endocytic recycling and provide new insights into the mechanisms by which tubular REs are generated.",
author = "Giridharan, {Sai Srinivas Panapakkam} and Bishuang Cai and Nicolas Vitale and Naava Naslavsky and Caplan, {Steven H}",
year = "2013",
month = "6",
day = "1",
doi = "10.1091/mbc.E13-01-0026",
language = "English (US)",
volume = "24",
pages = "1776--1790",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "11",

}

TY - JOUR

T1 - Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis

AU - Giridharan, Sai Srinivas Panapakkam

AU - Cai, Bishuang

AU - Vitale, Nicolas

AU - Naslavsky, Naava

AU - Caplan, Steven H

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Endocytic transport necessitates the generation of membrane tubules and their subsequent fission to transport vesicles for sorting of cargo molecules. The endocytic recycling compartment, an array of tubular and vesicular membranes decorated by the Eps15 homology domain protein, EHD1, is responsible for receptor and lipid recycling to the plasma membrane. It has been proposed that EHD dimers bind and bend membranes, thus generating recycling endosome (RE) tubules. However, recent studies show that molecules interacting with CasL-Like1 (MICAL-L1), a second, recently identified RE tubule marker, recruits EHD1 to preexisting tubules. The mechanisms and events supporting the generation of tubular recycling endosomes were unclear. Here, we propose a mechanism for the biogenesis of RE tubules. We demonstrate that MICAL-L1 and the BAR-domain protein syndapin2 bind to phosphatidic acid, which we identify as a novel lipid component of RE. Our studies demonstrate that direct interactions between these two proteins stabilize their association with membranes, allowing for nucleation of tubules by syndapin2. Indeed, the presence of phosphatidic acid in liposomes enhances the ability of syndapin2 to tubulate membranes in vitro. Overall our results highlight a new role for phosphatidic acid in endocytic recycling and provide new insights into the mechanisms by which tubular REs are generated.

AB - Endocytic transport necessitates the generation of membrane tubules and their subsequent fission to transport vesicles for sorting of cargo molecules. The endocytic recycling compartment, an array of tubular and vesicular membranes decorated by the Eps15 homology domain protein, EHD1, is responsible for receptor and lipid recycling to the plasma membrane. It has been proposed that EHD dimers bind and bend membranes, thus generating recycling endosome (RE) tubules. However, recent studies show that molecules interacting with CasL-Like1 (MICAL-L1), a second, recently identified RE tubule marker, recruits EHD1 to preexisting tubules. The mechanisms and events supporting the generation of tubular recycling endosomes were unclear. Here, we propose a mechanism for the biogenesis of RE tubules. We demonstrate that MICAL-L1 and the BAR-domain protein syndapin2 bind to phosphatidic acid, which we identify as a novel lipid component of RE. Our studies demonstrate that direct interactions between these two proteins stabilize their association with membranes, allowing for nucleation of tubules by syndapin2. Indeed, the presence of phosphatidic acid in liposomes enhances the ability of syndapin2 to tubulate membranes in vitro. Overall our results highlight a new role for phosphatidic acid in endocytic recycling and provide new insights into the mechanisms by which tubular REs are generated.

UR - http://www.scopus.com/inward/record.url?scp=84878686056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878686056&partnerID=8YFLogxK

U2 - 10.1091/mbc.E13-01-0026

DO - 10.1091/mbc.E13-01-0026

M3 - Article

VL - 24

SP - 1776

EP - 1790

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 11

ER -