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Drug
Enzyme
Compound
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Query: UMLS:C0038187 (
starvation
)
24,951
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
MCOLN3
/TRPML3 is a Ca
2+
-permeable cation channel that is expressed in multiple subcellular compartments with dynamic localization. Our previous studies suggest that upon macroautophagy/autophagy induction
MCOLN3
/TRPML3 is recruited and provides Ca
2+
for the fusion process in autophagosome biogenesis. However, how intracellular trafficking and the Ca
2+
channel function of
MCOLN3
/TRPML3 are related to autophagy are not known. Here we report that
MCOLN3
/TRPML3 undergoes palmitoylation at its C-terminal region, which is required for dynamic trafficking and cellular function of
MCOLN3
/TRPML3 in autophagy. Palmitoylation regulated
MCOLN3
/TRPML3 surface expression and trafficking, but not channel properties or localization and function of intracellular
MCOLN3
/TRPML3. Activation of intracellular
MCOLN3
/TRPML3 induced robust Ca
2+
release, which solely increased autophagy in Ca
2+
- and palmitoylation-dependent manners. Palmitoylation regulated not only intracellular
MCOLN3
/TRPML3 trafficking to autophagic structures but also autophagic flux in induced autophagy. Importantly, nutrient
starvation
activated
MCOLN3
/TRPML3 to release Ca
2+
and increased the level of
MCOLN3
/TRPML3 palmitoylation. Disruption of
MCOLN3
/TRPML3 palmitoylation, however, abolished the
starvation
-induced
MCOLN3
/TRPML3 activation without affecting channel activity. These results suggest that trafficking and channel function of
MCOLN3
/TRPML3 are regulated in the context of autophagy, and palmitoylation is a prerequisite for the function of
MCOLN3
/TRPML3 as a Ca
2+
channel in autophagosome formation by controlling its trafficking between subcellular compartments.
Abbreviations
: 17-ODYA, 17-octadecynoic acid; 2-BP, 2-bromopalmitate; BFA, brefeldin A; DN, dominant-negative; GPN, glycyl-L-phenylalanine-beta-naphthylamide; HN, hydroxylamine; KD, knockdown;
MCOLN3
/TRPML3, mucolipin 3; MS, mass spectrometry; PAT, palmitoyl acyltransferase; PM, plasma membrane; WT, wild type; ZDHHC, a zinc-finger motif and an Asp-His-His-Cys sequence.
...
PMID:Palmitoylation controls trafficking of the intracellular Ca
2+
channel MCOLN3/TRPML3 to regulate autophagy. 3021 88
