Cholesterol level regulates endosome motility via Rab proteins.

Abstract:

:The role of cholesterol in the regulation of endosome motility was investigated by monitoring the intracellular trafficking of endocytosed folate receptors (FRs) labeled with fluorescent folate conjugates. Real-time fluorescence imaging of HeLa cells transfected with green fluorescent protein-tubulin revealed that FR-containing endosomes migrate along microtubules. Moreover, microinjection with antibodies that inhibit microtubule-associated motor proteins demonstrated that dynein and kinesin I participate in the delivery of FR-containing endosomes to the perinuclear area and plasma membrane, respectively. Further, single-particle tracking analysis revealed bidirectional motions of FR endosomes, mediated by dynein and kinesin motors associated with the same endosome. These experimental tools allowed us to use FR-containing endosomes to evaluate the impact of cholesterol on intracellular membrane trafficking. Lowering plasma membrane cholesterol by metabolic depletion or methyl-beta-cyclodextrin extraction was found to both increase FR-containing endosome motility and change endosome distribution from colocalization with Rab7 to colocalization with Rab4. These data provide evidence that cholesterol regulates intracellular membrane trafficking via modulation of the distribution of low molecular weight G-proteins that are adaptors for microtubule motors.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Chen H,Yang J,Low PS,Cheng JX

doi

10.1529/biophysj.106.099366

subject

Has Abstract

pub_date

2008-02-15 00:00:00

pages

1508-20

issue

4

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(08)70666-0

journal_volume

94

pub_type

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