Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
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Target Concepts:
Gene/Protein
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Query: UMLS:C0038187 (
starvation
)
24,951
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To resolve the signaling mechanisms that mediate the
starvation
-induced processes of
Dictyostelium
sporulation and encystation, we performed insertional mutagenesis on cells harboring an mRFP-tagged spore gene. We isolated a mutant in
kinkyA
(
knkA
), a gene without known function, which formed fruiting bodies with a kinked stalk and lacking viable spores. Immunoprecipitation of lysates of KnkA-YFP-transformed
knkA
-
cells yielded a mammalian
BCAS3
homolog as a KnkA interactor.
bcas3
-
phenocopied
knkA
-
and Bcas3 colocalized with KnkA to puncta. Bcas3 shares sequence similarity with proppins (beta-propellors that bind phosphoinositides). Mutation of 2 Bcas3 residues that are essential for PtdIns3P binding in proppins prevented Bcas3 binding to PtdIns3P as well as punctate Bcas3 and KnkA localization. KnkA puncta also colocalized with small but not large vesicles that contain the autophagy protein Atg8 and were contiguous with the endoplasmic reticulum.
knkA
-
and
bcas3
-
cells showed a pronounced decrease of RFP-GFP-Atg8 in neutral early autophagosomes, indicating that KnkA and Bcas3 are required for macroautophagy/autophagy. Knockouts in
atg7, atg5
or
atg9
substantiated this finding by showing similar sporulation defects as
knkA
-
and
bcas3
-
. Defective
Dictyostelium
sporulation is evidently a useful diagnostic tool for the discovery of novel autophagy genes.
Abbreviations:
Atg: Autophagy-related;
BCAS3
:
BCAS3
microtubule associated cell migration factor; cAMP: 3',5'-cyclic adenosine monophosphate; ER: endoplasmic reticulum; GFP: green fluorescent protein; PAS: phagophore assembly site; PRKA/PKA: protein kinase cAMP-dependent; Proppin: beta-propellers that bind phosphoinositides; PtdIns3P: phosphatidylinositol 3-phosphate; REMI: restriction enzyme-mediated insertional mutagenesis; RFP: red fluorescent protein; RT-qPCR: reverse transcriptase - quantitative polymerase chain reaction; WIPI: WD repeat domain, phosphoinositide interacting; YFP: yellow fluorescent protein.
...
PMID:The proppin Bcas3 and its interactor KinkyA localize to the early phagophore and regulate autophagy. 3211 88
