LC3/GABARAP family proteins: autophagy-(un)related functions

From yeast to mammals, autophagy is an important mechanism for sustaining cellular homeostasis through facilitating the degradation and recycling of aged and cytotoxic components. During autophagy, cargo is captured in double-membraned vesicles, the autophagosomes, and degraded through lysosomal fus...

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Published inThe FASEB journal Vol. 30; no. 12; p. 3961
Main Authors Schaaf, Marco B E, Keulers, Tom G, Vooijs, Marc A, Rouschop, Kasper M A
Format Journal Article
LanguageEnglish
Published United States 01.12.2016
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ISSN1530-6860
DOI10.1096/fj.201600698R

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Abstract From yeast to mammals, autophagy is an important mechanism for sustaining cellular homeostasis through facilitating the degradation and recycling of aged and cytotoxic components. During autophagy, cargo is captured in double-membraned vesicles, the autophagosomes, and degraded through lysosomal fusion. In yeast, autophagy initiation, cargo recognition, cargo engulfment, and vesicle closure is Atg8 dependent. In higher eukaryotes, Atg8 has evolved into the LC3/GABARAP protein family, consisting of 7 family proteins [LC3A (2 splice variants), LC3B, LC3C, GABARAP, GABARAPL1, and GABARAPL2]. LC3B, the most studied family protein, is associated with autophagosome development and maturation and is used to monitor autophagic activity. Given the high homology, the other LC3/GABARAP family proteins are often presumed to fulfill similar functions. Nevertheless, substantial evidence shows that the LC3/GABARAP family proteins are unique in function and important in autophagy-independent mechanisms. In this review, we discuss the current knowledge and functions of the LC3/GABARAP family proteins. We focus on processing of the individual family proteins and their role in autophagy initiation, cargo recognition, vesicle closure, and trafficking, a complex and tightly regulated process that requires selective presentation and recruitment of these family proteins. In addition, functions unrelated to autophagy of the LC3/GABARAP protein family members are discussed.-Schaaf, M. B. E., Keulers, T. G, Vooijs, M. A., Rouschop, K. M. A. LC3/GABARAP family proteins: autophagy-(un)related functions.
AbstractList From yeast to mammals, autophagy is an important mechanism for sustaining cellular homeostasis through facilitating the degradation and recycling of aged and cytotoxic components. During autophagy, cargo is captured in double-membraned vesicles, the autophagosomes, and degraded through lysosomal fusion. In yeast, autophagy initiation, cargo recognition, cargo engulfment, and vesicle closure is Atg8 dependent. In higher eukaryotes, Atg8 has evolved into the LC3/GABARAP protein family, consisting of 7 family proteins [LC3A (2 splice variants), LC3B, LC3C, GABARAP, GABARAPL1, and GABARAPL2]. LC3B, the most studied family protein, is associated with autophagosome development and maturation and is used to monitor autophagic activity. Given the high homology, the other LC3/GABARAP family proteins are often presumed to fulfill similar functions. Nevertheless, substantial evidence shows that the LC3/GABARAP family proteins are unique in function and important in autophagy-independent mechanisms. In this review, we discuss the current knowledge and functions of the LC3/GABARAP family proteins. We focus on processing of the individual family proteins and their role in autophagy initiation, cargo recognition, vesicle closure, and trafficking, a complex and tightly regulated process that requires selective presentation and recruitment of these family proteins. In addition, functions unrelated to autophagy of the LC3/GABARAP protein family members are discussed.-Schaaf, M. B. E., Keulers, T. G, Vooijs, M. A., Rouschop, K. M. A. LC3/GABARAP family proteins: autophagy-(un)related functions.
Author Keulers, Tom G
Schaaf, Marco B E
Vooijs, Marc A
Rouschop, Kasper M A
Author_xml – sequence: 1
  givenname: Marco B E
  surname: Schaaf
  fullname: Schaaf, Marco B E
  organization: Department of Radiation Oncology (Maastro Lab), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
– sequence: 2
  givenname: Tom G
  surname: Keulers
  fullname: Keulers, Tom G
  organization: Department of Radiation Oncology (Maastro Lab), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
– sequence: 3
  givenname: Marc A
  surname: Vooijs
  fullname: Vooijs, Marc A
  organization: Department of Radiation Oncology (Maastro Lab), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
– sequence: 4
  givenname: Kasper M A
  surname: Rouschop
  fullname: Rouschop, Kasper M A
  email: kasper.rouschop@maastrichtuniversity.nl
  organization: Department of Radiation Oncology (Maastro Lab), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands kasper.rouschop@maastrichtuniversity.nl
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27601442$$D View this record in MEDLINE/PubMed
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ATG7
autophagosome
Atg8 orthologues
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Snippet From yeast to mammals, autophagy is an important mechanism for sustaining cellular homeostasis through facilitating the degradation and recycling of aged and...
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SubjectTerms Adaptor Proteins, Signal Transducing - metabolism
Animals
Autophagy - physiology
Homeostasis - physiology
Humans
Microtubule-Associated Proteins - metabolism
Protein Transport - physiology
Saccharomyces cerevisiae - metabolism
Title LC3/GABARAP family proteins: autophagy-(un)related functions
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