MLN64 is involved in actin-mediated dynamics of late endocytic organelles

Research output: Contribution to journalArticleScientificpeer-review

Abstract

MLN64 is a late endosomal cholesterol-binding membrane protein of an unknown function. Here, we show that MLN64 depletion results in the dispersion of late endocytic organelles to the cell periphery similarly as upon pharmacological actin disruption. The dispersed organelles in MLN64 knockdown cells exhibited decreased association with actin and the Arp2/3 complex subunit p34-Arc. MLN64 depletion was accompanied by impaired fusion of late endocytic organelles and delayed cargo degradation. MLN64 overexpression increased the number of actin and p34-Arc-positive patches on late endosomes, enhanced the fusion of late endocytic organelles in an actin-dependent manner, and stimulated the deposition of sterol in late endosomes harboring the protein. Overexpression of wild-type MLN64 was capable of rescuing the endosome dispersion in MLN64-depleted cells, whereas mutants of MLN64 defective in cholesterol binding were not, suggesting a functional connection between MLN64-mediated sterol transfer and actin-dependent late endosome dynamics. We propose that local sterol enrichment by MLN64 in the late endosomal membranes facilitates their association with actin, thereby governing actin-dependent fusion and degradative activity of late endocytic organelles.
Original languageEnglish
JournalMolecular Biology of the Cell
Volume16
Pages (from-to)3873-3886
Number of pages14
ISSN1059-1524
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

Cite this

@article{482059c1e8364f389657fe708d1dc987,
title = "MLN64 is involved in actin-mediated dynamics of late endocytic organelles",
abstract = "MLN64 is a late endosomal cholesterol-binding membrane protein of an unknown function. Here, we show that MLN64 depletion results in the dispersion of late endocytic organelles to the cell periphery similarly as upon pharmacological actin disruption. The dispersed organelles in MLN64 knockdown cells exhibited decreased association with actin and the Arp2/3 complex subunit p34-Arc. MLN64 depletion was accompanied by impaired fusion of late endocytic organelles and delayed cargo degradation. MLN64 overexpression increased the number of actin and p34-Arc-positive patches on late endosomes, enhanced the fusion of late endocytic organelles in an actin-dependent manner, and stimulated the deposition of sterol in late endosomes harboring the protein. Overexpression of wild-type MLN64 was capable of rescuing the endosome dispersion in MLN64-depleted cells, whereas mutants of MLN64 defective in cholesterol binding were not, suggesting a functional connection between MLN64-mediated sterol transfer and actin-dependent late endosome dynamics. We propose that local sterol enrichment by MLN64 in the late endosomal membranes facilitates their association with actin, thereby governing actin-dependent fusion and degradative activity of late endocytic organelles.",
author = "Maarit H{\"o}ltt{\"a}-Vuori and Fabien Alpy and Kimmo Tanhuanp{\"a}{\"a} and Eija Jokitalo and Aino-Liisa Mutka and Elina Ikonen",
year = "2005",
doi = "10.1091/mbc.E04-12-1105",
language = "English",
volume = "16",
pages = "3873--3886",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "AMERICAN SOCIETY FOR CELL BIOLOGY",

}

MLN64 is involved in actin-mediated dynamics of late endocytic organelles. / Hölttä-Vuori, Maarit; Alpy, Fabien; Tanhuanpää, Kimmo; Jokitalo, Eija; Mutka, Aino-Liisa; Ikonen, Elina.

In: Molecular Biology of the Cell, Vol. 16, 2005, p. 3873-3886.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - MLN64 is involved in actin-mediated dynamics of late endocytic organelles

AU - Hölttä-Vuori, Maarit

AU - Alpy, Fabien

AU - Tanhuanpää, Kimmo

AU - Jokitalo, Eija

AU - Mutka, Aino-Liisa

AU - Ikonen, Elina

PY - 2005

Y1 - 2005

N2 - MLN64 is a late endosomal cholesterol-binding membrane protein of an unknown function. Here, we show that MLN64 depletion results in the dispersion of late endocytic organelles to the cell periphery similarly as upon pharmacological actin disruption. The dispersed organelles in MLN64 knockdown cells exhibited decreased association with actin and the Arp2/3 complex subunit p34-Arc. MLN64 depletion was accompanied by impaired fusion of late endocytic organelles and delayed cargo degradation. MLN64 overexpression increased the number of actin and p34-Arc-positive patches on late endosomes, enhanced the fusion of late endocytic organelles in an actin-dependent manner, and stimulated the deposition of sterol in late endosomes harboring the protein. Overexpression of wild-type MLN64 was capable of rescuing the endosome dispersion in MLN64-depleted cells, whereas mutants of MLN64 defective in cholesterol binding were not, suggesting a functional connection between MLN64-mediated sterol transfer and actin-dependent late endosome dynamics. We propose that local sterol enrichment by MLN64 in the late endosomal membranes facilitates their association with actin, thereby governing actin-dependent fusion and degradative activity of late endocytic organelles.

AB - MLN64 is a late endosomal cholesterol-binding membrane protein of an unknown function. Here, we show that MLN64 depletion results in the dispersion of late endocytic organelles to the cell periphery similarly as upon pharmacological actin disruption. The dispersed organelles in MLN64 knockdown cells exhibited decreased association with actin and the Arp2/3 complex subunit p34-Arc. MLN64 depletion was accompanied by impaired fusion of late endocytic organelles and delayed cargo degradation. MLN64 overexpression increased the number of actin and p34-Arc-positive patches on late endosomes, enhanced the fusion of late endocytic organelles in an actin-dependent manner, and stimulated the deposition of sterol in late endosomes harboring the protein. Overexpression of wild-type MLN64 was capable of rescuing the endosome dispersion in MLN64-depleted cells, whereas mutants of MLN64 defective in cholesterol binding were not, suggesting a functional connection between MLN64-mediated sterol transfer and actin-dependent late endosome dynamics. We propose that local sterol enrichment by MLN64 in the late endosomal membranes facilitates their association with actin, thereby governing actin-dependent fusion and degradative activity of late endocytic organelles.

U2 - 10.1091/mbc.E04-12-1105

DO - 10.1091/mbc.E04-12-1105

M3 - Article

VL - 16

SP - 3873

EP - 3886

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

ER -