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Cited by 267Autophagy in Disease and TherapyCellular transport and secretionMicrotubule and mitosis dynamics

The Cytoskeleton-Autophagy Connection

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Kast, David J., Dominguez, Roberto·2017·Current Biology
DOI 10.1016/j.cub.2017.02.061PMC PMC5444402
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Abstract

Actin cytoskeleton dynamics play vital roles in most forms of intracellular trafficking by promoting the biogenesis and transport of vesicular cargoes. Mounting evidence indicates that actin dynamics and membrane-cytoskeleton scaffolds also have essential roles in macroautophagy, the process by which cellular waste is isolated inside specialized vesicles called autophagosomes for recycling and degradation. Branched actin polymerization is necessary for the biogenesis of autophagosomes from the endoplasmic reticulum (ER) membrane. Actomyosin-based transport is then used to feed the growing phagophore with pre-selected cargoes and debris derived from different membranous organelles inside the cell. Finally, mature autophagosomes detach from the ER membrane by an as yet unknown mechanism, undergo intracellular transport and then fuse with lysosomes, endosomes and multivesicular bodies through mechanisms that involve actin- and microtubule-mediated motility, cytoskeleton-membrane scaffolds and signaling proteins. In this review, we highlight the considerable progress made recently towards understanding the diverse roles of the cytoskeleton in autophagy.

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  • The biogenesis and trafficking of autophagosomes are highly dependent on cytoskeletal dynamics, including actin assembly, membrane-cytoskeletal scaffolds, and actomyosin-based transport.

    “The biogenesis and trafficking of autophagosomes are highly dependent on cytoskeletal dynamics, including actin assembly, membrane–cytoskeletal scaffolds, and actomyosin-based transport [148].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [148]

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  1. [1]Anitei M Hoflack B 2011 Bridging membrane and cytoskeleton dynamics in the secretory and endocytic pathways Nat Cell Biol 14 11 19 22193159
  2. [2]Suetsugu S Gautreau A 2012 Synergistic BAR-NPF interactions in actin-driven membrane remodeling Trends Cell Biol 22 141 150 22306177
  3. [3]Kaksonen M Toret CP Drubin DG 2006 Harnessing actin dynamics for clathrin-mediated endocytosis Nat Rev Mol Cell Biol 7 404 414 16723976
  4. [4]Egea G Lazaro-Dieguez F Vilella M 2006 Actin dynamics at the Golgi complex in mammalian cells Curr Opin Cell Biol 18 168 178 16488588
  5. [5]Coutts AS La Thangue NB 2015 Actin nucleation by WH2 domains at the autophagosome Nat Commun 6 7888 26223951 PMC4532831
  6. [6]Kast DJ Dominguez R 2015 WHAMM links actin assembly via the Arp2/3 complex to autophagy Autophagy 11 1702 1704 26291929 PMC4590594
  7. [7]Kast DJ Zajac AL Holzbaur EL Ostap EM Dominguez R 2015 WHAMM Directs the Arp2/3 Complex to the ER for Autophagosome Biogenesis through an Actin Comet Tail Mechanism Curr Biol 25 1791 1797 26096974 PMC4489997
  8. [8]Mi N Chen Y Wang S Chen M Zhao M Yang G Ma M Su Q Luo S Shi J 2015 CapZ regulates autophagosomal membrane shaping by promoting actin assembly inside the isolation membrane Nat Cell Biol 17 1112 1123 26237647
  9. [9]Ariosa AR Klionsky DJ 2016 Autophagy core machinery: overcoming spatial barriers in neurons J Mol Med (Berl) 94 1217 1227 27544281 PMC5071157
  10. [10]Reggiori F Komatsu M Finley K Simonsen A 2012 Autophagy: more than a nonselective pathway Int J Cell Biol 2012 219625 22666256 PMC3362037
  11. [12]Menzies FM Fleming A Rubinsztein DC 2015 Compromised autophagy and neurodegenerative diseases Nat Rev Neurosci 16 345 357 25991442
  12. [14]Choi AM Ryter SW Levine B 2013 Autophagy in human health and disease N Engl J Med 368 651 662 23406030
  13. [15]Wong PM Puente C Ganley IG Jiang X 2013 The ULK1 complex: sensing nutrient signals for autophagy activation Autophagy 9 124 137 23295650 PMC3552878
  14. [16]Jean S Kiger AA 2014 Classes of phosphoinositide 3-kinases at a glance J Cell Sci 127 923 928 24587488 PMC3937771
  15. [17]Axe EL Walker SA Manifava M Chandra P Roderick HL Habermann A Griffiths G Ktistakis NT 2008 Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum J Cell Biol 182 685 701 18725538 PMC2518708
  16. [18]Yla-Anttila P Vihinen H Jokitalo E Eskelinen EL 2009 3D tomography reveals connections between the phagophore and endoplasmic reticulum Autophagy 5 1180 1185 19855179
  17. [20]Knaevelsrud H Soreng K Raiborg C Haberg K Rasmuson F Brech A Liestol K Rusten TE Stenmark H Neufeld TP 2013 Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation J Cell Biol 202 331 349 23878278 PMC3718966
  18. [21]Puri C Renna M Bento CF Moreau K Rubinsztein DC 2013 Diverse autophagosome membrane sources coalesce in recycling endosomes Cell 154 1285 1299 24034251 PMC3791395
  19. [22]Longatti A Tooze SA 2012 Recycling endosomes contribute to autophagosome formation Autophagy 8 1682 1683 22874560 PMC3494599
  20. [23]Hailey DW Rambold AS Satpute-Krishnan P Mitra K Sougrat R Kim PK Lippincott-Schwartz J 2010 Mitochondria supply membranes for autophagosome biogenesis during starvation Cell 141 656 667 20478256 PMC3059894
  21. [24]Yamamoto H Kakuta S Watanabe TM Kitamura A Sekito T Kondo-Kakuta C Ichikawa R Kinjo M Ohsumi Y 2012 Atg9 vesicles are an important membrane source during early steps of autophagosome formation J Cell Biol 198 219 233 22826123 PMC3410421
  22. [26]Ge L Melville D Zhang M Schekman R 2013 The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis Elife 2 e00947 23930225 PMC3736544
  23. [27]Hamasaki M Shibutani ST Yoshimori T 2013 Up-to-date membrane biogenesis in the autophagosome formation Curr Opin Cell Biol 25 455 460 23578367
  24. [28]Ichimura Y Kirisako T Takao T Satomi Y Shimonishi Y Ishihara N Mizushima N Tanida I Kominami E Ohsumi M 2000 A ubiquitin-like system mediates protein lipidation Nature 408 488 492 11100732
  25. [29]Rubinsztein DC Cuervo AM Ravikumar B Sarkar S Korolchuk V Kaushik S Klionsky DJ 2009 In search of an “autophagomometer” Autophagy 5 585 589 19411822
  26. [30]Fujita N Itoh T Omori H Fukuda M Noda T Yoshimori T 2008 The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy Mol Biol Cell 19 2092 2100 18321988 PMC2366860
  27. [31]Wild P McEwan DG Dikic I 2014 The LC3 interactome at a glance J Cell Sci 127 3 9 24345374
  28. [33]Verlhac P Gregoire IP Azocar O Petkova DS Baguet J Viret C Faure M 2015 Autophagy receptor NDP52 regulates pathogen-containing autophagosome maturation Cell Host Microbe 17 515 525 25771791
  29. [34]Wild P Farhan H McEwan DG Wagner S Rogov VV Brady NR Richter B Korac J Waidmann O Choudhary C 2011 Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth Science 333 228 233 21617041 PMC3714538
  30. [35]Tumbarello DA Manna PT Allen M Bycroft M Arden SD Kendrick-Jones J Buss F 2015 The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy PLoS Pathog 11 e1005174 26451915 PMC4599966
  31. [36]Kirkin V Lamark T Sou YS Bjorkoy G Nunn JL Bruun JA Shvets E McEwan DG Clausen TH Wild P 2009 A role for NBR1 in autophagosomal degradation of ubiquitinated substrates Mol Cell 33 505 516 19250911
  32. [37]Fujita N Hayashi-Nishino M Fukumoto H Omori H Yamamoto A Noda T Yoshimori T 2008 An Atg4B mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure Mol Biol Cell 19 4651 4659 18768752 PMC2575160
  33. [38]Mauvezin C Nagy P Juhasz G Neufeld TP 2015 Autophagosome-lysosome fusion is independent of V-ATPase-mediated acidification Nat Commun 6 7007 25959678 PMC4428688
  34. [39]Fader CM Colombo MI 2009 Autophagy and multivesicular bodies: two closely related partners Cell Death Differ 16 70 78 19008921
  35. [40]Saftig P Klumperman J 2009 Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function Nat Rev Mol Cell Biol 10 623 635 19672277
  36. [41]Aplin A Jasionowski T Tuttle DL Lenk SE Dunn WA Jr 1992 Cytoskeletal elements are required for the formation and maturation of autophagic vacuoles J Cell Physiol 152 458 466 1506410
  37. [42]Aguilera MO Beron W Colombo MI 2012 The actin cytoskeleton participates in the early events of autophagosome formation upon starvation induced autophagy Autophagy 8 1590 1603 22863730 PMC3494589
  38. [43]Reggiori F Monastyrska I Shintani T Klionsky DJ 2005 The actin cytoskeleton is required for selective types of autophagy, but not nonspecific autophagy, in the yeast Saccharomyces cerevisiae Mol Biol Cell 16 5843 5856 16221887 PMC1289426
  39. [44]Zhuo C Ji Y Chen Z Kitazato K Xiang Y Zhong M Wang Q Pei Y Ju H Wang Y 2013 Proteomics analysis of autophagy-deficient Atg7−/−MEFs reveals a close relationship between F-actin and autophagy Biochem Biophys Res Commun 437 482 488 23850690
  40. [45]Xia P Wang S Du Y Zhao Z Shi L Sun L Huang G Ye B Li C Dai Z 2013 WASH inhibits autophagy through suppression of Beclin 1 ubiquitination EMBO J 32 2685 2696 23974797 PMC3801434
  41. [46]Zavodszky E Seaman MN Moreau K Jimenez-Sanchez M Breusegem SY Harbour ME Rubinsztein DC 2014 Mutation in VPS35 associated with Parkinson’s disease impairs WASH complex association and inhibits autophagy Nat Commun 5 3828 24819384 PMC4024763
  42. [47]Moreau K Ghislat G Hochfeld W Renna M Zavodszky E Runwal G Puri C Lee S Siddiqi F Menzies FM 2015 Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy Nat Commun 6 8045 26289944 PMC4560779
  43. [48]Dominguez R 2016 The WH2 Domain and Actin Nucleation: Necessary but Insufficient Trends Biochem Sci 41 478 490 27068179 PMC4884163
  44. [49]Rotty JD Wu C Bear JE 2013 New insights into the regulation and cellular functions of the ARP2/3 complex Nat Rev Mol Cell Biol 14 7 12 23212475
  45. [50]Lamason RL Welch MD 2016 Actin-based motility and cell-to-cell spread of bacterial pathogens Curr Opin Microbiol 35 48 57 27997855 PMC5474209
  46. [52]King JS Gueho A Hagedorn M Gopaldass N Leuba F Soldati T Insall RH 2013 WASH is required for lysosomal recycling and efficient autophagic and phagocytic digestion Mol Biol Cell 24 2714 2726 23885127 PMC3756923
  47. [53]Wang P Richardson C Hawes C Hussey PJ 2016 Arabidopsis NAP1 Regulates the Formation of Autophagosomes Curr Biol 26 2060 2069 27451899
  48. [54]Campellone KG Webb NJ Znameroski EA Welch MD 2008 WHAMM is an Arp2/3 complex activator that binds microtubules and functions in ER to Golgi transport Cell 134 148 161 18614018 PMC2556884
  49. [55]Zuchero JB Coutts AS Quinlan ME Thangue NB Mullins RD 2009 p53-cofactor JMY is a multifunctional actin nucleation factor Nat Cell Biol 11 451 459 19287377 PMC2763628
  50. [56]Kruppa AJ Kendrick-Jones J Buss F 2016 Myosins, Actin and Autophagy Traffic 17 878 890 27146966 PMC4957615
  51. [57]Greenberg MJ Ostap EM 2013 Regulation and control of myosin-I by the motor and light chain-binding domains Trends Cell Biol 23 81 89 23200340 PMC3558615
  52. [58]Brandstaetter H Kendrick-Jones J Buss F 2012 Myo1c regulates lipid raft recycling to control cell spreading, migration and Salmonella invasion J Cell Sci 125 1991 2003 22328521 PMC3360920
  53. [60]Brandstaetter H Kishi-Itakura C Tumbarello DA Manstein DJ Buss F 2014 Loss of functional MYO1C/myosin 1c, a motor protein involved in lipid raft trafficking, disrupts autophagosome-lysosome fusion Autophagy 10 2310 2323 25551774 PMC4502697
  54. [61]Cordonnier MN Dauzonne D Louvard D Coudrier E 2001 Actin filaments and myosin I alpha cooperate with microtubules for the movement of lysosomes Mol Biol Cell 12 4013 4029 11739797 PMC60772
  55. [62]Ma X Adelstein RS 2014 The role of vertebrate nonmuscle Myosin II in development and human disease Bioarchitecture 4 88 102 25098841 PMC4201603
  56. [63]Miserey-Lenkei S Chalancon G Bardin S Formstecher E Goud B Echard A 2010 Rab and actomyosin-dependent fission of transport vesicles at the Golgi complex Nat Cell Biol 12 645 654 20562865
  57. [64]Tang HW Wang YB Wang SL Wu MH Lin SY Chen GC 2011 Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy EMBO J 30 636 651 21169990 PMC3041946
  58. [65]Buss F Spudich G Kendrick-Jones J 2004 Myosin VI: cellular functions and motor properties Annu Rev Cell Dev Biol 20 649 676 15473855
  59. [67]Rusten TE Stenmark H 2009 How do ESCRT proteins control autophagy? J Cell Sci 122 2179 2183 19535733
  60. [69]Geeraert C Ratier A Pfisterer SG Perdiz D Cantaloube I Rouault A Pattingre S Proikas-Cezanne T Codogno P Pous C 2010 Starvation-induced hyperacetylation of tubulin is required for the stimulation of autophagy by nutrient deprivation J Biol Chem 285 24184 24194 20484055 PMC2911293
  61. [70]Jahreiss L Menzies FM Rubinsztein DC 2008 The itinerary of autophagosomes: from peripheral formation to kiss-and-run fusion with lysosomes Traffic 9 574 587 18182013 PMC2329914
  62. [71]Kimura S Noda T Yoshimori T 2008 Dynein-dependent movement of autophagosomes mediates efficient encounters with lysosomes Cell Struct Funct 33 109 122 18388399
  63. [72]Fass E Shvets E Degani I Hirschberg K Elazar Z 2006 Microtubules support production of starvation-induced autophagosomes but not their targeting and fusion with lysosomes J Biol Chem 281 36303 36316 16963441
  64. [73]Kochl R Hu XW Chan EY Tooze SA 2006 Microtubules facilitate autophagosome formation and fusion of autophagosomes with endosomes Traffic 7 129 145 16420522
  65. [74]Maday S Holzbaur EL 2014 Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway Dev Cell 30 71 85 25026034 PMC4109719
  66. [75]Du W Su QP Chen Y Zhu Y Jiang D Rong Y Zhang S Zhang Y Ren H Zhang C 2016 Kinesin 1 Drives Autolysosome Tubulation Dev Cell 37 326 336 27219061
  67. [76]McMahon HT Boucrot E 2015 Membrane curvature at a glance J Cell Sci 128 1065 1070 25774051 PMC4359918
  68. [77]Khan MM Strack S Wild F Hanashima A Gasch A Brohm K Reischl M Carnio S Labeit D Sandri M 2014 Role of autophagy, SQSTM1, SH3GLB1, and TRIM63 in the turnover of nicotinic acetylcholine receptors Autophagy 10 123 136 24220501 PMC4389866
  69. [78]Zhuang X Wang H Lam SK Gao C Wang X Cai Y Jiang L 2013 A BAR-domain protein SH3P2, which binds to phosphatidylinositol 3-phosphate and ATG8, regulates autophagosome formation in Arabidopsis Plant Cell 25 4596 4615 24249832 PMC3875738
  70. [79]Gerke V Creutz CE Moss SE 2005 Annexins: linking Ca2+ signalling to membrane dynamics Nat Rev Mol Cell Biol 6 449 461 15928709
  71. [80]Hayes MJ Rescher U Gerke V Moss SE 2004 Annexin-actin interactions Traffic 5 571 576 15260827
  72. [81]Ghislat G Aguado C Knecht E 2012 Annexin A5 stimulates autophagy and inhibits endocytosis J Cell Sci 125 92 107 22266906
  73. [82]Carlsson SR Simonsen A 2015 Membrane dynamics in autophagosome biogenesis J Cell Sci 128 193 205 25568151
  74. [84]Diao J Liu R Rong Y Zhao M Zhang J Lai Y Zhou Q Wilz LM Li J Vivona S 2015 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes Nature 520 563 566 25686604 PMC4442024
  75. [85]Kaufmann A Beier V Franquelim HG Wollert T 2014 Molecular mechanism of autophagic membrane-scaffold assembly and disassembly Cell 156 469 481 24485455
  76. [86]Ridley AJ 2015 Rho GTPase signalling in cell migration Curr Opin Cell Biol 36 103 112 26363959 PMC4728192
  77. [87]Mleczak A Millar S Tooze SA Olson MF Chan EY 2013 Regulation of autophagosome formation by Rho kinase Cell Signal 25 1 11 22975682
  78. [88]Ao X Zou L Wu Y 2014 Regulation of autophagy by the Rab GTPase network Cell Death Differ 21 348 358 24440914 PMC3921601
  79. [89]Russo AJ Mathiowetz AJ Hong S Welch MD Campellone KG 2016 Rab1 recruits WHAMM during membrane remodeling but limits actin nucleation Mol Biol Cell 27 967 978 26823012 PMC4791140
  80. [90]Zoppino FC Militello RD Slavin I Alvarez C Colombo MI 2010 Autophagosome formation depends on the small GTPase Rab1 and functional ER exit sites Traffic 11 1246 1261 20545908
  81. [91]Hayashi-Nishino M Fujita N Noda T Yamaguchi A Yoshimori T Yamamoto A 2009 A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation Nat Cell Biol 11 1433 1437 19898463
  82. [92]Lazarou M Sliter DA Kane LA Sarraf SA Wang C Burman JL Sideris DP Fogel AI Youle RJ 2015 The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy Nature 524 309 314 26266977 PMC5018156
  83. [93]Tang D Kang R Zeh HJ 3rd Lotze MT 2011 High-mobility group box 1, oxidative stress, and disease Antioxid Redox Signal 14 1315 1335 20969478 PMC3048826
  84. [94]Mostowy S 2014 Multiple roles of the cytoskeleton in bacterial autophagy PLoS Pathog 10 e1004409 25412422 PMC4239108

Cited by

Sorted by citations

Authors
Kast, D. J., & Dominguez, R.
Affiliations
University of Pennsylvania (US)
Corresponding author
Kast, David J.
ORCID
Kast, David J.
Venue
Current Biology
Publisher
Elsevier BV
Published
2017-04
Volume
27
Issue
8
Pages
R318-R326
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2017.02.061
PMC
PMC5444402
OpenAlex
W2608038215
Cited by
267
References
10
Citations by year
2026: 18 · 2025: 28 · 2024: 40 · 2023: 33 · 2022: 31 · 2021: 38 · 2020: 20 · 2019: 32 · 2018: 21 · 2017: 6
FWCI
2.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (P01GM087253)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
actin cytoskeleton, autophagy, macroautophagy, autophagosome formation, branched actin polymerization, endoplasmic reticulum membrane, phagophore, lysosome fusion, microtubules, intracellular trafficking, multivesicular bodies
MeSH terms
Animals, Autophagy, Cytoskeleton, Humans, Phagosomes, Protein Transport

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