Versatile role of the yeast ubiquitin ligase Rsp5p in intracellular trafficking

2008 ◽  
Vol 36 (5) ◽  
pp. 791-796 ◽  
Author(s):  
Naima Belgareh-Touzé ◽  
Sébastien Léon ◽  
Zoi Erpapazoglou ◽  
Marta Stawiecka-Mirota ◽  
Danièle Urban-Grimal ◽  
...  

The ubiquitin ligase (E3) Rsp5p is the only member of the Nedd (neural-precursor-cell-expressed, developmentally down-regulated) 4 family of E3s present in yeast. Rsp5p has several proteasome-independent functions in membrane protein trafficking, including a role in the ubiquitination of most plasma membrane proteins, leading to their endocytosis. Rsp5p is also required for the ubiquitination of endosomal proteins, leading to their sorting to the internal vesicles of MVBs (multivesicular bodies). Rsp5p catalyses the attachment of non-conventional ubiquitin chains, linked through ubiquitin Lys-63, to some endocytic and MVB cargoes. This modification appears to be required for efficient sorting, possibly because these chains have a greater affinity for the ubiquitin-binding domains present within endocytic or MVB sorting complexes. The mechanisms involved in the recognition of plasma membrane and MVB substrates by Rsp5p remain unclear. A subset of Rsp5/Nedd4 substrates have a ‘PY motif’ and are recognized directly by the WW (Trp-Trp) domains of Rsp5p. Most Rsp5p substrates do not carry PY motifs, but some may depend on PY-containing proteins for their ubiquitination by Rsp5p, consistent with the latter's acting as specificity factors or adaptors. As in other ubiquitin-conjugating systems, these adaptors are also Rsp5p substrates and undergo ubiquitin-dependent trafficking. In the present review, we discuss recent examples illustrating the role of Rsp5p in membrane protein trafficking and providing new insights into the regulation of this E3 by adaptor proteins.

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Muqing Cao ◽  
Jue Ning ◽  
Carmen I Hernandez-Lara ◽  
Olivier Belzile ◽  
Qian Wang ◽  
...  

The role of the primary cilium in key signaling pathways depends on dynamic regulation of ciliary membrane protein composition, yet we know little about the motors or membrane events that regulate ciliary membrane protein trafficking in existing organelles. Recently, we showed that cilium-generated signaling in Chlamydomonas induced rapid, anterograde IFT-independent, cytoplasmic microtubule-dependent redistribution of the membrane polypeptide, SAG1-C65, from the plasma membrane to the periciliary region and the ciliary membrane. Here, we report that the retrograde IFT motor, cytoplasmic dynein 1b, is required in the cytoplasm for this rapid redistribution. Furthermore, signaling-induced trafficking of SAG1-C65 into cilia is unidirectional and the entire complement of cellular SAG1-C65 is shed during signaling and can be recovered in the form of ciliary ectosomes that retain signal-inducing activity. Thus, during signaling, cells regulate ciliary membrane protein composition through cytoplasmic action of the retrograde IFT motor and shedding of ciliary ectosomes.


2004 ◽  
Vol 165 (1) ◽  
pp. 135-144 ◽  
Author(s):  
Rebecca Dunn ◽  
Deborah A. Klos ◽  
Adam S. Adler ◽  
Linda Hicke

Ubiquitin ligases of the Nedd4 family regulate membrane protein trafficking by modifying both cargo proteins and the transport machinery with ubiquitin. Here, we investigate the role of the yeast Nedd4 homologue, Rsp5, in protein sorting into vesicles that bud into the multivesicular endosome (MVE) en route to the vacuole. A mutant lacking the Rsp5 C2 domain is unable to ubiquitinate or sort biosynthetic cargo into MVE vesicles, whereas endocytic cargo is ubiquitinated and sorted efficiently. The C2 domain binds specifically to phosphoinositides in vitro and is sufficient for localization to membranes in intact cells. Mutation of a lysine-rich patch on the surface of the C2 domain abolishes membrane interaction and disrupts sorting of biosynthetic cargo. Translational fusion of ubiquitin to a biosynthetic cargo protein alleviates the requirement for the C2 domain in its MVE sorting. These results demonstrate that the C2 domain specifies Rsp5-dependent ubiquitination of endosomal cargo and suggest that Rsp5 function is regulated by membrane phosphoinositides.


2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Katarina Mackovicova ◽  
Annemieke T Goot ◽  
Klaas A Sjollema ◽  
Ellen AA Nollen ◽  
Sven CD Ijzendoorn

2013 ◽  
Vol 104 (2) ◽  
pp. 619a
Author(s):  
Philip D. Fox ◽  
Christpher J. Haberkorn ◽  
Aubrey V. Weigel ◽  
Elizabeth J. Akin ◽  
Matthew J. Kennedy ◽  
...  

2012 ◽  
Vol 24 (7) ◽  
pp. 3074-3086 ◽  
Author(s):  
Elena Feraru ◽  
Mugurel I. Feraru ◽  
Rin Asaoka ◽  
Tomasz Paciorek ◽  
Riet De Rycke ◽  
...  

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