title: An ESCRT-spastin interaction promotes fission of recycling tubules from the endosome.
abstract: Mechanisms coordinating endosomal degradation and recycling are poorly understood, as are the cellular roles of microtubule (MT) severing. We show that cells lacking the MT-severing protein spastin had increased tubulation of and defective receptor sorting through endosomal tubular recycling compartments. Spastin required the ability to sever MTs and to interact with ESCRT-III (a complex controlling cargo degradation) proteins to regulate endosomal tubulation. Cells lacking IST1 (increased sodium tolerance 1), an endosomal sorting complex required for transport (ESCRT) component to which spastin binds, also had increased endosomal tubulation. Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery. Spastin is mutated in the axonopathy hereditary spastic paraplegia. Zebrafish spinal motor axons depleted of spastin or IST1 also had abnormal endosomal tubulation, so we propose this phenotype is important for axonal degeneration.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge CB2 0XY, England, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Allison
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Lumb
authors.forename: Coralie
authors.initials: C
authors.lastname: Fassier
authors.forename: James W
authors.initials: JW
authors.lastname: Connell
authors.forename: Daniel
authors.initials: D
authors.lastname: Ten Martin
authors.forename: Matthew N J
authors.initials: MN
authors.lastname: Seaman
authors.forename: Jamilé
authors.initials: J
authors.lastname: Hazan
authors.forename: Evan
authors.initials: E
authors.lastname: Reid
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D000074181:Spastin; D015027:Zebrafish
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C533705:IST1 protein, human; D015513:Oncogene Proteins; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human
references.citation: J Neurochem. 2009 Mar;108(5):1277-88
references.pmid: 19141076
references.citation: Nature. 2009 Mar 12;458(7235):172-7
references.pmid: 19234443
references.citation: Biochem Soc Trans. 2010 Dec;38(6):1397-412
references.pmid: 21118097
references.citation: Traffic. 2010 Apr;11(4):508-19
references.pmid: 20070609
references.citation: Hum Mol Genet. 2006 Jan 15;15(2):307-18
references.pmid: 16339213
references.citation: Cell. 2012 Mar 30;149(1):124-36
references.pmid: 22464325
references.citation: J Cell Sci. 2010 Nov 1;123(Pt 21):3703-17
references.pmid: 20923837
references.citation: Dev Cell. 2009 Jul;17(1):110-22
references.pmid: 19619496
references.citation: Dev Cell. 2008 Jan;14(1):6-8
references.pmid: 18194647
references.citation: Dev Cell. 2009 Nov;17(5):712-23
references.pmid: 19922875
references.citation: Curr Opin Cell Biol. 2008 Aug;20(4):427-36
references.pmid: 18472259
references.citation: Dev Cell. 2011 Jul 19;21(1):77-91
references.pmid: 21763610
references.citation: Nat Cell Biol. 2007 Dec;9(12):1370-80
references.pmid: 17994011
references.citation: Biochim Biophys Acta. 2012 Jan;1823(1):192-7
references.pmid: 21888932
references.citation: Hum Mol Genet. 2005 Jan 1;14(1):19-38
references.pmid: 15537668
references.citation: Cell. 2009 Apr 17;137(2):191-6
references.pmid: 19379681
references.citation: J Cell Biol. 2010 Aug 23;190(4):565-74
references.pmid: 20733053
references.citation: Nat Genet. 1999 Nov;23(3):296-303
references.pmid: 10610178
references.citation: EMBO J. 2006 Jun 7;25(11):2275-86
references.pmid: 16688221
references.citation: Curr Opin Cell Biol. 2009 Aug;21(4):568-74
references.pmid: 19560911
references.citation: Dev Cell. 2002 Aug;3(2):271-82
references.pmid: 12194857
references.citation: Nat Rev Neurosci. 2011 Jan;12(1):31-42
references.pmid: 21139634
references.citation: J Cell Sci. 1996 Apr;109 ( Pt 4):749-62
references.pmid: 8718666
references.citation: Dev Cell. 2009 Nov;17(5):699-711
references.pmid: 19922874
references.citation: Hum Mol Genet. 2006 Sep 15;15(18):2763-71
references.pmid: 16893913
references.citation: J Clin Invest. 2010 Apr;120(4):1097-110
references.pmid: 20200447
references.citation: Crit Rev Biochem Mol Biol. 2010 Dec;45(6):463-87
references.pmid: 20653365
references.citation: Hum Mol Genet. 2009 Oct 15;18(20):3805-21
references.pmid: 19620182
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19140-5
references.pmid: 17146056
references.citation: Traffic. 2012 Jan;13(1):94-107
references.pmid: 21973056
references.citation: Mol Biol Cell. 2009 Mar;20(5):1374-87
references.pmid: 19129480
references.citation: Dev Cell. 2002 Aug;3(2):283-9
references.pmid: 12194858
references.citation: Dis Model Mech. 2013 Jan;6(1):72-83
references.pmid: 22773755
references.citation: J Cell Biol. 2012 Jun 25;197(7):971-82
references.pmid: 22711696
references.citation: Mol Biol Cell. 2009 Mar;20(5):1360-73
references.pmid: 19129479
references.citation: Nat Neurosci. 2007 Feb;10(2):177-85
references.pmid: 17220882
references.citation: Exp Cell Res. 2005 Oct 1;309(2):358-69
references.pmid: 16026783
references.citation: Dev Dyn. 1995 Jul;203(3):253-310
references.pmid: 8589427
references.citation: Traffic. 2007 Aug;8(8):1068-79
references.pmid: 17547705
references.citation: J Cell Biol. 2003 Sep 1;162(5):909-18
references.pmid: 12952941
references.citation: Curr Biol. 2004 Oct 26;14(20):1791-800
references.pmid: 15498486
references.citation: Cell. 2012 Oct 12;151(2):356-71
references.pmid: 23063125
references.citation: Mol Biol Cell. 2012 Nov;23(21):4226-41
references.pmid: 22956769
references.citation: Nat Struct Mol Biol. 2008 Dec;15(12):1278-86
references.pmid: 18997780
references.citation: Science. 2011 Mar 25;331(6024):1616-20
references.pmid: 21310966
references.citation: Development. 2005 Oct;132(20):4471-81
references.pmid: 16162647
references.citation: Nature. 2007 Oct 11;449(7163):740-4
references.pmid: 17928862
references.citation: Nat Cell Biol. 2011 Jun;13(6):715-21
references.pmid: 21602791
references.citation: Nature. 2007 Oct 11;449(7163):735-9
references.pmid: 17928861
references.citation: Nat Neurosci. 2010 Nov;13(11):1380-7
references.pmid: 20935645
references.citation: Annu Rev Cell Dev Biol. 2007;23:519-47
references.pmid: 17506697
references.citation: Nat Rev Mol Cell Biol. 2004 Feb;5(2):121-32
references.pmid: 15040445
references.citation: Traffic. 2009 Jan;10(1):42-56
references.pmid: 19000169
references.citation: Traffic. 2012 Mar;13(3):468-82
references.pmid: 22118530
references.citation: Mol Biol Cell. 2004 Aug;15(8):3530-41
references.pmid: 15181150
references.citation: Nat Struct Mol Biol. 2009 Jul;16(7):754-62
references.pmid: 19525971
references.citation: Mol Biol Cell. 2010 Oct 1;21(19):3293-303
references.pmid: 20719964
references.citation: Nature. 2008 Jan 17;451(7176):363-7
references.pmid: 18202664
references.citation: J Clin Invest. 2012 Feb;122(2):538-44
references.pmid: 22232211
references.citation: J Cell Biol. 2004 Apr;165(1):111-22
references.pmid: 15078902
references.citation: Cell. 2009 Aug 7;138(3):549-61
references.pmid: 19665976