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@ARTICLE{Park:165146,
author = {Park, Jae-Sook and Hu, Yiying and Hollingsworth, Nancy M
and Miltenberger-Miltenyi, Gabriel and Neiman, Aaron M},
title = {{I}nteraction between {VPS}13{A} and the {XK} scramblase is
important for {VPS}13{A} function in humans.},
journal = {Journal of cell science},
volume = {135},
number = {17},
issn = {0021-9533},
address = {Cambridge},
publisher = {Company of Biologists Limited},
reportid = {DZNE-2022-01451},
pages = {jcs260227},
year = {2022},
abstract = {VPS13 family proteins form conduits between the membranes
of different organelles through which lipids are
transferred. In humans, there are four VPS13 paralogs, and
mutations in the genes encoding each of them are associated
with different inherited disorders. VPS13 proteins contain
multiple conserved domains. The Vps13 adaptor-binding (VAB)
domain binds to adaptor proteins that recruit VPS13 to
specific membrane contact sites. This work demonstrates the
importance of a different domain in VPS13A function. The
pleckstrin homology (PH) domain at the C-terminal region of
VPS13A is required to form a complex with the XK scramblase
and for the co-localization of VPS13A with XK within the
cell. Alphafold modeling was used to predict an interaction
surface between VPS13A and XK. Mutations in this region
disrupt both complex formation and co-localization of the
two proteins. Mutant VPS13A alleles found in patients with
VPS13A disease truncate the PH domain. The phenotypic
similarities between VPS13A disease and McLeod syndrome
caused by mutations in VPS13A and XK, respectively, argue
that loss of the VPS13A-XK complex is the basis of both
diseases.},
keywords = {Humans / Mitochondrial Membranes: metabolism / Mutation:
genetics / Neuroacanthocytosis: complications /
Neuroacanthocytosis: genetics / Neuroacanthocytosis:
metabolism / Vesicular Transport Proteins: genetics /
Vesicular Transport Proteins: metabolism / Lipid transport
(Other) / Neuro-acanthocytosis syndromes (Other) /
Neurodegeneration (Other) / PH domain (Other) / VPS13A
(Other) / XK (Other) / VPS13A protein, human (NLM Chemicals)
/ Vesicular Transport Proteins (NLM Chemicals)},
cin = {Zebrafish Models ; AG Schmid München},
ddc = {570},
cid = {I:(DE-2719)1140002},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9482346},
pubmed = {pmid:35950506},
doi = {10.1242/jcs.260227},
url = {https://pub.dzne.de/record/165146},
}