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Microtubule-dependent and independent roles of spastin in lipid droplet dispersion and biogenesis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Microtubule-dependent and independent roles of spastin in lipid droplet dispersion and biogenesis.
Συγγραφείς: Tadepalle N; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Robers L; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Veronese M; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Zentis P; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Babatz F; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Brodesser S; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Gruszczyk AV; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Schauss A; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany., Höning S; Institute for Biochemistry I, University of Cologne, Cologne, Germany., Rugarli EI; Institute for Genetics, University of Cologne, Cologne, Germany elena.rugarli@uni-koeln.de.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
Πηγή: Life science alliance [Life Sci Alliance] 2020 Apr 22; Vol. 3 (6). Date of Electronic Publication: 2020 Apr 22 (Print Publication: 2020).
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE
Imprint Name(s): Original Publication: [Woodbury, NY] : Life Science Alliance, LLC, [2018]-
Ιατρικοί όροι (MeSH): Endoplasmic Reticulum/*metabolism , Lipid Droplets/*metabolism , Microtubules/*metabolism , Signal Transduction/*genetics , Spastic Paraplegia, Hereditary/*metabolism , Spastin/*deficiency, Fibroblasts/metabolism ; Motor Neurons/metabolism ; Spastic Paraplegia, Hereditary/genetics ; Spastin/genetics ; Triglycerides/metabolism ; Animals ; Cell Line, Tumor ; Gene Knockout Techniques ; HEK293 Cells ; Humans ; Isoenzymes ; Mice ; Mutation ; Transfection
Περίληψη: Lipid droplets (LDs) are metabolic organelles that store neutral lipids and dynamically respond to changes in energy availability by accumulating or mobilizing triacylglycerols (TAGs). How the plastic behavior of LDs is regulated is poorly understood. Hereditary spastic paraplegia is a central motor axonopathy predominantly caused by mutations in SPAST, encoding the microtubule-severing protein spastin. The spastin-M1 isoform localizes to nascent LDs in mammalian cells; however, the mechanistic significance of this targeting is not fully explained. Here, we show that tightly controlled levels of spastin-M1 are required to inhibit LD biogenesis and TAG accumulation. Spastin-M1 maintains the morphogenesis of the ER when TAG synthesis is prevented, independent from microtubule binding. Moreover, spastin plays a microtubule-dependent role in mediating the dispersion of LDs from the ER upon glucose starvation. Our results reveal a dual role of spastin to shape ER tubules and to regulate LD movement along microtubules, opening new perspectives for the pathogenesis of hereditary spastic paraplegia.
(© 2020 Tadepalle et al.)
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Substance Nomenclature: 0 (Isoenzymes)
0 (Triglycerides)
EC 3.6.4.3 (Spastin)
EC 5.6.1.1 (SPAST protein, human)
EC 5.6.1.1 (Spast protein, mouse)
Entry Date(s): Date Created: 20200424 Date Completed: 20210707 Latest Revision: 20210707
Update Code: 20260130
PubMed Central ID: PMC7184029
DOI: 10.26508/lsa.202000715
PMID: 32321733
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2575-1077
DOI:10.26508/lsa.202000715