Calcineurin-dependent regulation of endocytosis by a plasma membrane ubiquitin ligase adaptor, Rcr1

Lu Zhu; Richa Sardana; Daniel K Jin; Scott D Emr

doi:10.1083/jcb.201909158

Calcineurin-dependent regulation of endocytosis by a plasma membrane ubiquitin ligase adaptor, Rcr1

J Cell Biol. 2020 Aug 3;219(8):e201909158. doi: 10.1083/jcb.201909158.

Authors

Lu Zhu^{1

2}, Richa Sardana^{1

2}, Daniel K Jin^{1

2}, Scott D Emr^{1

2}

Affiliations

¹ Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY.
² Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY.

Abstract

Rsp5, the Nedd4 family member in yeast, is an E3 ubiquitin ligase involved in numerous cellular processes, many of which require Rsp5 to interact with PY-motif containing adaptor proteins. Here, we show that two paralogous transmembrane Rsp5 adaptors, Rcr1 and Rcr2, are sorted to distinct cellular locations: Rcr1 is a plasma membrane (PM) protein, whereas Rcr2 is sorted to the vacuole. Rcr2 is delivered to the vacuole using ubiquitin as a sorting signal. Rcr1 is delivered to the PM by the exomer complex using a newly uncovered PM sorting motif. Further, we show that Rcr1, but not Rcr2, is up-regulated via the calcineurin/Crz1 signaling pathway. Upon exogenous calcium treatment, Rcr1 ubiquitinates and down-regulates the chitin synthase Chs3. We propose that the PM-anchored Rsp5/Rcr1 ubiquitin ligase-adaptor complex can provide an acute response to degrade unwanted proteins under stress conditions, thereby maintaining cell integrity.

MeSH terms

Calcineurin / genetics
Calcineurin / metabolism*
Chitin Synthase / genetics
Chitin Synthase / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Endocytosis*
Endosomal Sorting Complexes Required for Transport / genetics
Endosomal Sorting Complexes Required for Transport / metabolism*
Gene Expression Regulation, Fungal
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Protein Sorting Signals
Proteolysis
Saccharomyces cerevisiae / enzymology*
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Signal Transduction
Transcription Factors / genetics
Transcription Factors / metabolism
Ubiquitin-Protein Ligase Complexes / genetics
Ubiquitin-Protein Ligase Complexes / metabolism*
Ubiquitination

Substances

CNB1 protein, S cerevisiae
CRZ1 protein, S cerevisiae
DNA-Binding Proteins
Endosomal Sorting Complexes Required for Transport
Membrane Proteins
Protein Sorting Signals
Rcr1 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Transcription Factors
Ubiquitin-Protein Ligase Complexes
CHS3 protein, S cerevisiae
Chitin Synthase
Calcineurin
RSP5 protein, S cerevisiae