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PMID: 20357004 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RNF-121 is an endoplasmic reticulum-membrane E3 ubiquitin ligase involved in the regulation of beta-integrin.

Molecular biology of the cell ·Vol. 21 ·No. 11 ·2010-06-01 ·Pages 1788-98

Darom A, Bening-Abu-Shach U, Broday L

Abstract

We report on the characterization of RNF-121, an evolutionarily conserved E3 ligase RING finger protein that is expressed in the endoplasmic reticulum (ER) of various cells and tissues in Caenorhabditis elegans. Inactivation of RNF-121 induced an elevation in BiP expression and increased the sensitivity of worms to ER stress. Genetic analysis placed RNF-121 downstream of the unfolded protein response (UPR) regulator protein kinase-like endoplasmic reticulum kinase (PERK). We identify PAT-3::GFP, the beta subunit of the heterodimeric integrin receptors, as an RNF-121 substrate; whereas induction of RNF-121 expression reduced the level of PAT-3::GFP in the gonad distal tip cells, inhibition of RNF-121 led to the accumulation of stably bound PAT-3::GFP inclusions. Correspondingly, overexpression of RNF-121 during early stages of gonad development led to aberrations in germline development and gonad migration that overlap with those observed after PAT-3 inactivation. The formation of these gonad abnormalities required functional ER-associated degradation (ERAD) machinery. Our findings identify RNF-121 as an ER-anchored ubiquitin ligase that plays a specific role in the ERAD pathway by linking it to the regulation of the cell adhesion integrin receptors.

MeSH Terms
Animals Animals, Genetically Modified Caenorhabditis elegans/anatomy & histology,metabolism Caenorhabditis elegans Proteins/genetics,metabolism Cell Cycle Proteins/genetics,metabolism Endoplasmic Reticulum/enzymology Gonads/abnormalities,metabolism Heat-Shock Proteins/genetics,metabolism Integrin beta Chains/genetics,metabolism MAP Kinase Kinase 1/genetics,metabolism RING Finger Domains RNA Interference Recombinant Fusion Proteins/genetics,metabolism Signal Transduction/physiology Stress, Physiological Ubiquitin-Protein Ligases/genetics,metabolism eIF-2 Kinase/genetics,metabolism
Chemicals
Caenorhabditis elegans Proteins Cell Cycle Proteins Heat-Shock Proteins Hsp-4 protein, C elegans Integrin beta Chains Recombinant Fusion Proteins pat-3 protein, C elegans RNF-121 protein, C elegans Ubiquitin-Protein Ligases PERK kinase eIF-2 Kinase pek-1 protein, C elegans MAP Kinase Kinase 1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Darom Amir
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Bening-Abu-Shach Ulrike
Broday Limor
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e09-09-0774
Published
2010-06-01
Epub
2010-00-31
Pages
1788-98
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2877638
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e09-09-0774 PMC Full Text View journal details
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