Tadepalle, Nimesha, Robers, Lennart, Veronese, Matteo, Zentis, Peter ORCID: 0000-0002-6999-132X, Babatz, Felix, Brodesser, Susanne, Gruszczyk, Anja, V, Schauss, Astrid, Hoening, Stefan and Rugarli, Elena, I ORCID: 0000-0002-5782-1067 (2020). Microtubule-dependent and independent roles of spastin in lipid droplet dispersion and biogenesis. Life Sci. Alliance, 3 (6). COLD SPRING HARBOR: LIFE SCIENCE ALLIANCE LLC. ISSN 2575-1077

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tadepalle, NimeshaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robers, LennartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veronese, MatteoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zentis, PeterUNSPECIFIEDorcid.org/0000-0002-6999-132XUNSPECIFIED
Babatz, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brodesser, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruszczyk, Anja, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schauss, AstridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoening, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rugarli, Elena, IUNSPECIFIEDorcid.org/0000-0002-5782-1067UNSPECIFIED
URN: urn:nbn:de:hbz:38-331184
DOI: 10.26508/lsa.202000715
Journal or Publication Title: Life Sci. Alliance
Volume: 3
Number: 6
Date: 2020
Publisher: LIFE SCIENCE ALLIANCE LLC
Place of Publication: COLD SPRING HARBOR
ISSN: 2575-1077
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ENDOPLASMIC-RETICULUM; PARAPLEGIA PROTEIN; SEVERING ENZYMES; ATLASTIN GTPASES; ER; TRANSPORT; INCREASE; REVEAL; GROWTH; EXPRESSIONMultiple languages
BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/33118

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