Home LiteratureArticle Details
PMID: 18287533 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Arp2 links autophagic machinery with the actin cytoskeleton.

Molecular biology of the cell ·Vol. 19 ·No. 5 ·2008-05-00 ·Pages 1962-75

Monastyrska I, He C, Geng J, Hoppe AD, Li Z, Klionsky DJ

Abstract

Macroautophagy involves lysosomal/vacuolar elimination of long-lived proteins and entire organelles from the cytosol. The process begins with formation of a double-membrane vesicle that sequesters bulk cytoplasm, or a specific cargo destined for lysosomal/vacuolar delivery. The completed vesicle fuses with the lysosome/vacuole limiting membrane, releasing its content into the organelle lumen for subsequent degradation and recycling of the resulting macromolecules. A majority of the autophagy-related (Atg) proteins are required at the step of vesicle formation. The integral membrane protein Atg9 cycles between certain intracellular compartments and the vesicle nucleation site, presumably to supply membranes necessary for macroautophagic vesicle formation. In this study we have tracked the movement of Atg9 over time in living cells by using real-time fluorescence microscopy. Our results reveal that an actin-related protein, Arp2, briefly colocalizes with Atg9 and directly regulates the dynamics of Atg9 movement. We propose that proteins of the Arp2/3 complex regulate Atg9 transport for specific types of autophagy.

MeSH Terms
Actin-Related Protein 2/metabolism Actin-Related Protein 2-3 Complex/metabolism Actins/metabolism Autophagy Autophagy-Related Proteins Cytoskeleton/metabolism Membrane Proteins/metabolism Mutation/genetics Protein Binding Protein Transport Saccharomyces cerevisiae/cytology,metabolism Saccharomyces cerevisiae Proteins/metabolism Vesicular Transport Proteins/metabolism
Chemicals
ARP2 protein, S cerevisiae ATG9 protein, S cerevisiae Actin-Related Protein 2 Actin-Related Protein 2-3 Complex Actins Atg11 protein, S cerevisiae Autophagy-Related Proteins Membrane Proteins Saccharomyces cerevisiae Proteins Vesicular Transport Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Monastyrska Iryna
Life Sciences Institute and Departments of Molecular, Cellular, University of Michigan, Ann Arbor, MI 48109, USA.
He Congcong
Geng Jiefei
Hoppe Adam D
Li Zhijian
Klionsky Daniel J
References (54)
54 references, click to expand
  1. Endoplasmic reticulum stress triggers autophagy.
    J Biol Chem. 2006 Oct 6;281(40):30299-304 PMID: 16901900
  2. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton.
    Nat Rev Mol Cell Biol. 2007 Jan;8(1):37-48 PMID: 17183359
  3. Regulation of actin filament assembly by Arp2/3 complex and formins.
    Annu Rev Biophys Biomol Struct. 2007;36:451-77 PMID: 17477841
  4. The role of autophagy in mitochondria maintenance: characterization of mitochondrial functions in autophagy-deficient S. cerevisiae strains.
    Autophagy. 2007 Jul-Aug;3(4):337-46 PMID: 17404498
  5. Autophagosomes: biogenesis from scratch?
    Curr Opin Cell Biol. 2005 Aug;17(4):415-22 PMID: 15978794
  6. Atg22 recycles amino acids to link the degradative and recycling functions of autophagy.
    Mol Biol Cell. 2006 Dec;17(12):5094-104 PMID: 17021250
  7. The complex containing actin-related proteins Arp2 and Arp3 is required for the motility and integrity of yeast actin patches.
    Curr Biol. 1997 Jul 1;7(7):519-29 PMID: 9210376
  8. Protein turnover via autophagy: implications for metabolism.
    Annu Rev Nutr. 2007;27:19-40 PMID: 17311494
  9. Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases.
    Mol Cell Biol. 1988 Nov;8(11):4936-48 PMID: 3062374
  10. A protein complex containing Mdm10p, Mdm12p, and Mmm1p links mitochondrial membranes and DNA to the cytoskeleton-based segregation machinery.
    Mol Biol Cell. 2003 Nov;14(11):4618-27 PMID: 13679517
  11. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.
    Yeast. 1998 Jul;14(10):953-61 PMID: 9717241
  12. Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway.
    J Biol Chem. 2004 Jul 16;279(29):29889-94 PMID: 15138258
  13. Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome.
    J Cell Biol. 1997 Dec 29;139(7):1687-95 PMID: 9412464
  14. Structural aspects of autophagy.
    Adv Exp Med Biol. 1996;389:103-11 PMID: 8860999
  15. Development by self-digestion: molecular mechanisms and biological functions of autophagy.
    Dev Cell. 2004 Apr;6(4):463-77 PMID: 15068787
  16. Vesicles carry most exocyst subunits to exocytic sites marked by the remaining two subunits, Sec3p and Exo70p.
    J Cell Biol. 2004 Dec 6;167(5):889-901 PMID: 15583031
  17. Recruitment of Atg9 to the preautophagosomal structure by Atg11 is essential for selective autophagy in budding yeast.
    J Cell Biol. 2006 Dec 18;175(6):925-35 PMID: 17178909
  18. Autophagy: molecular machinery for self-eating.
    Cell Death Differ. 2005 Nov;12 Suppl 2:1542-52 PMID: 16247502
  19. The two faces of autophagy: Coxiella and Mycobacterium.
    Autophagy. 2006 Jul-Sep;2(3):162-4 PMID: 16874070
  20. Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex.
    J Cell Biol. 2001 Jan 8;152(1):51-64 PMID: 11149920
  21. Live cell imaging of mitochondrial movement along actin cables in budding yeast.
    Curr Biol. 2004 Nov 23;14(22):1996-2004 PMID: 15556861
  22. The yeast actin-related protein Arp2p is required for the internalization step of endocytosis.
    Mol Biol Cell. 1997 Jul;8(7):1361-75 PMID: 9243513
  23. Autophagy.
    Curr Biol. 2005 Apr 26;15(8):R282-3 PMID: 15854889
  24. Cvt18/Gsa12 is required for cytoplasm-to-vacuole transport, pexophagy, and autophagy in Saccharomyces cerevisiae and Pichia pastoris.
    Mol Biol Cell. 2001 Dec;12(12):3821-38 PMID: 11739783
  25. Yeast Eps15-like endocytic protein, Pan1p, activates the Arp2/3 complex.
    Nat Cell Biol. 2001 Jul;3(7):687-90 PMID: 11433303
  26. Dissection of Arp2/3 complex actin nucleation mechanism and distinct roles for its nucleation-promoting factors in Saccharomyces cerevisiae.
    Genetics. 2005 Sep;171(1):35-47 PMID: 16183906
  27. Cytoskeletal elements are required for the formation and maturation of autophagic vacuoles.
    J Cell Physiol. 1992 Sep;152(3):458-66 PMID: 1506410
  28. Coupling actin dynamics to the endocytic process in Saccharomyces cerevisiae.
    Protoplasma. 2005 Oct;226(1-2):81-8 PMID: 16231104
  29. Autophagy in health and disease: a double-edged sword.
    Science. 2004 Nov 5;306(5698):990-5 PMID: 15528435
  30. Pexophagy: the selective autophagy of peroxisomes.
    Autophagy. 2005 Jul;1(2):75-83 PMID: 16874024
  31. Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast.
    Genetics. 1996 Dec;144(4):1425-36 PMID: 8978031
  32. A unified nomenclature for yeast autophagy-related genes.
    Dev Cell. 2003 Oct;5(4):539-45 PMID: 14536056
  33. Starvation triggers the delivery of the endoplasmic reticulum to the vacuole via autophagy in yeast.
    Traffic. 2005 Jan;6(1):56-65 PMID: 15569245
  34. Sorting of proteins into multivesicular bodies: ubiquitin-dependent and -independent targeting.
    EMBO J. 2001 Sep 17;20(18):5176-86 PMID: 11566881
  35. Phosphoregulation of Arp2/3-dependent actin assembly during receptor-mediated endocytosis.
    Nat Cell Biol. 2005 Mar;7(3):246-54 PMID: 15711538
  36. A novel fluorescence-activated cell sorter-based screen for yeast endocytosis mutants identifies a yeast homologue of mammalian eps15.
    J Cell Biol. 1996 Dec;135(6 Pt 1):1485-500 PMID: 8978817
  37. Atg17 regulates the magnitude of the autophagic response.
    Mol Biol Cell. 2005 Jul;16(7):3438-53 PMID: 15901835
  38. The actin cytoskeleton is required for selective types of autophagy, but not nonspecific autophagy, in the yeast Saccharomyces cerevisiae.
    Mol Biol Cell. 2005 Dec;16(12):5843-56 PMID: 16221887
  39. Selective and non-selective autophagic degradation of mitochondria in yeast.
    Autophagy. 2007 Jul-Aug;3(4):329-36 PMID: 17377488
  40. Aminopeptidase I is targeted to the vacuole by a nonclassical vesicular mechanism.
    J Cell Biol. 1997 Jul 14;138(1):37-44 PMID: 9214379
  41. Actin-binding proteins.
    J Cell Sci. 2005 Feb 15;118(Pt 4):651-4 PMID: 15701920
  42. Potential therapeutic applications of autophagy.
    Nat Rev Drug Discov. 2007 Apr;6(4):304-12 PMID: 17396135
  43. Endocytic vesicle scission by lipid phase boundary forces.
    Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10277-10282 PMID: 16801551
  44. Regulation of N-WASP and the Arp2/3 complex by Abp1 controls neuronal morphology.
    PLoS One. 2007 May 02;2(5):e400 PMID: 17476322
  45. The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation.
    EMBO J. 2001 Nov 1;20(21):5971-81 PMID: 11689437
  46. Atg27 is required for autophagy-dependent cycling of Atg9.
    Mol Biol Cell. 2007 Feb;18(2):581-93 PMID: 17135291
  47. Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation.
    Science. 1998 Jul 3;281(5373):105-8 PMID: 9651243
  48. A cycling protein complex required for selective autophagy.
    Autophagy. 2007 Sep-Oct;3(5):422-32 PMID: 17426440
  49. Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts.
    Autophagy. 2005 Jul;1(2):101-9 PMID: 16874040
  50. Arp2/3 complex and actin dynamics are required for actin-based mitochondrial motility in yeast.
    Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3162-7 PMID: 11248049
  51. Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway.
    Dev Cell. 2002 Dec;3(6):825-37 PMID: 12479808
  52. Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway.
    J Cell Biol. 1992 Oct;119(2):287-99 PMID: 1400574
  53. Autophagy recognizes intracellular Salmonella enterica serovar Typhimurium in damaged vacuoles.
    Autophagy. 2006 Jul-Sep;2(3):156-8 PMID: 16874057
  54. Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy.
    Mol Biol Cell. 2003 Feb;14(2):477-90 PMID: 12589048
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e07-09-0892
Published
2008-05-00
Epub
2008-00-20
Pages
1962-75
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2366845
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053396 · United States
NIGMS NIH HHS · GM-53396 · United States
External Links
PubMed source DOI: 10.1091/mbc.e07-09-0892 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2