A dominant negative form of the AAA ATPase SKD1/VPS4 impairs membrane trafficking out of endosomal/lysosomal compartments: class E vps phenotype in mammalian cells - PubMed (original) (raw)
. 2003 Jan 15;116(Pt 2):401-14.
doi: 10.1242/jcs.00213.
Affiliations
- PMID: 12482925
- DOI: 10.1242/jcs.00213
A dominant negative form of the AAA ATPase SKD1/VPS4 impairs membrane trafficking out of endosomal/lysosomal compartments: class E vps phenotype in mammalian cells
Hideaki Fujita et al. J Cell Sci. 2003.
Abstract
SKD1 is a member of the family of ATPases associated with cellular activities whose yeast homologue Vps4p has been implicated in endosomal/vacuolar membrane transports. When a mutant of SKD1 that lacks ATPase activity [SKD1(E235Q)] was overexpressed in mammalian cells, it induced a dominant negative phenotype characterized by aberrant endosomal structures (denoted as E235Q compartments). Expression of SKD1(E235Q) caused an accumulation of basolateral recycling receptors, such as asialoglycoprotein receptor and low-density lipoprotein in polarized hepatocytes and Madin-Darby canine kidney cells, respectively, in E235Q compartments. In addition, SKD1(E235Q) also abrogated, via endosomes, transport to the trans-Golgi network, as indicated by an accumulation of TGN38 in E235Q compartments. Three lines of evidence further demonstrated that SKD1 participates in the membrane transport from early endosomes to late endosomes/lysosomes: (1) a redistribution of a late endosomal and lysosomal membrane protein endolyn in E235Q compartments; (2) an inhibition of epidermal growth factor receptor degradation, due to an accumulation of the receptors in E235Q compartments; and (3) a mis-sorting of and defect in the proteolytic processing of newly synthesized cathepsin D. An intriguing finding was that the expression of SKD1(E235Q) caused the number of lysosomes to decrease (to one-sixth of control numbers) but their size to increase (2.4-fold larger in diameter than control lysosomes). Indeed, an ultrastructural analysis revealed that the expression of SKD1(E235Q) causes an accumulation of hybrid organelles formed by direct fusion between late endosomes and lysosomes. We conclude that SKD1 regulates multiple steps of membrane transport out of early endosomes and the reformation of lysosomes from a hybrid organelle.
Similar articles
- The mouse SKD1, a homologue of yeast Vps4p, is required for normal endosomal trafficking and morphology in mammalian cells.
Yoshimori T, Yamagata F, Yamamoto A, Mizushima N, Kabeya Y, Nara A, Miwako I, Ohashi M, Ohsumi M, Ohsumi Y. Yoshimori T, et al. Mol Biol Cell. 2000 Feb;11(2):747-63. doi: 10.1091/mbc.11.2.747. Mol Biol Cell. 2000. PMID: 10679028 Free PMC article. - Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B.
Fujita H, Umezuki Y, Imamura K, Ishikawa D, Uchimura S, Nara A, Yoshimori T, Hayashizaki Y, Kawai J, Ishidoh K, Tanaka Y, Himeno M. Fujita H, et al. J Cell Sci. 2004 Jun 15;117(Pt 14):2997-3009. doi: 10.1242/jcs.01170. Epub 2004 Jun 1. J Cell Sci. 2004. PMID: 15173323 - SKD1 AAA ATPase-dependent endosomal transport is involved in autolysosome formation.
Nara A, Mizushima N, Yamamoto A, Kabeya Y, Ohsumi Y, Yoshimori T. Nara A, et al. Cell Struct Funct. 2002 Feb;27(1):29-37. doi: 10.1247/csf.27.29. Cell Struct Funct. 2002. PMID: 11937716 - ESCRT and Membrane Protein Ubiquitination.
Migliano SM, Teis D. Migliano SM, et al. Prog Mol Subcell Biol. 2018;57:107-135. doi: 10.1007/978-3-319-96704-2_4. Prog Mol Subcell Biol. 2018. PMID: 30097773 Review. - Maturation of autophagic vacuoles in Mammalian cells.
Eskelinen EL. Eskelinen EL. Autophagy. 2005 Apr;1(1):1-10. doi: 10.4161/auto.1.1.1270. Epub 2005 Apr 28. Autophagy. 2005. PMID: 16874026 Review.
Cited by
- Small GTPase Rab12 regulates transferrin receptor degradation: Implications for a novel membrane trafficking pathway from recycling endosomes to lysosomes.
Matsui T, Fukuda M. Matsui T, et al. Cell Logist. 2011 Jul;1(4):155-158. doi: 10.4161/cl.1.4.18152. Epub 2011 Jul 1. Cell Logist. 2011. PMID: 22279614 Free PMC article. - Mutational analysis of Candida albicans SNF7 reveals genetically separable Rim101 and ESCRT functions and demonstrates divergence in bro1-domain protein interactions.
Wolf JM, Davis DA. Wolf JM, et al. Genetics. 2010 Mar;184(3):673-94. doi: 10.1534/genetics.109.112029. Epub 2009 Dec 21. Genetics. 2010. PMID: 20026677 Free PMC article. - Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent interactor of mucolipin-1.
Vergarajauregui S, Martina JA, Puertollano R. Vergarajauregui S, et al. J Biol Chem. 2009 Dec 25;284(52):36357-36366. doi: 10.1074/jbc.M109.047241. Epub 2009 Oct 28. J Biol Chem. 2009. PMID: 19864416 Free PMC article. - Exosomal MicroRNAs as Novel Cell-Free Therapeutics in Tissue Engineering and Regenerative Medicine.
Zeng EZ, Chen I, Chen X, Yuan X. Zeng EZ, et al. Biomedicines. 2022 Oct 5;10(10):2485. doi: 10.3390/biomedicines10102485. Biomedicines. 2022. PMID: 36289747 Free PMC article. Review. - Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer.
Gudi RR, Janakiraman H, Howe PH, Palanisamy V, Vasu C. Gudi RR, et al. Oncotarget. 2021 Apr 13;12(8):807-822. doi: 10.18632/oncotarget.27932. eCollection 2021 Apr 13. Oncotarget. 2021. PMID: 33889303 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials