Function of Hrs in endocytic trafficking and signalling

Raiborg, Camilla; Bache, Kristi G.; Mehlum, Anja; Stenmark, Harald

doi:10.1042/bst0290472

Cited by 47 publications

(45 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since EGF is known to be associated with its receptor along the degradative endocytic pathway, this could be due to the retention of ubiquitylated EGF-receptor and its ligand within a Hrs-containing sorting machinery capable of ubiquitin binding but incapable of Journal of Cell Science 119 (12) binding clathrin. Deleting the clathrin-box motif, which is only five amino acid residues in the extreme C-terminus of Hrs, does not change the ability of Hrs to bind any of its known interactors other than clathrin, such as STAM, Eps 15 or Tsg101 (Raiborg et al, 2001b;Bache et al, 2003a), and is thus a specific means of studying the effect of clathrin binding without interfering with other interactions.…”

Section: Discussionmentioning

confidence: 99%

Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains

Raiborg

Wesche

Malerød

et al. 2006

Journal of Cell Science

Self Cite

137

118

View full text Add to dashboard Cite

Endocytosed membrane proteins that are destined for degradation in lysosomes are ubiquitylated and recognised by sorting complexes on endosome membranes. The ubiquitin-binding sorting component Hrs as well as ubiquitylated cargo are enriched in a characteristic flat clathrin coat on the endosome membrane. The function of clathrin within this coat has not been investigated. Here, we show that both clathrin and the clathrin-box motif of Hrs are required for the clustering of Hrs into restricted microdomains. The C-terminus of Hrs, which contains the clathrin-box, is sufficient to redirect a phosphatidylinositol(3)-phosphate-binding protein into the Hrs- and clathrin-containing microdomains. Although these microdomains show little lateral diffusion in the membrane, they are dynamic structures that exchange Hrs and clathrin with similar kinetics, and acquire the downstream sorting component Tsg101. The clathrin-mediated clustering is essential for the function of Hrs in degradative protein sorting. We conclude that clathrin is responsible for concentrating Hrs in endosomal microdomains specialised for recognition of ubiquitylated membrane proteins, thus enabling efficient sorting of cargo into the degradative pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains

Raiborg

Wesche

Malerød

et al. 2006

Journal of Cell Science

Self Cite

137

118

View full text Add to dashboard Cite

show abstract

“…7B,C). Although to a lesser extent, Hrs, a marker of multivesicular bodies (Raiborg et al, 2001) (Fig. 7B,g,k), and Rab7, a marker of late endosomes (Marois et al, 2006) (not shown), also accumulated in rbsn 34 clones.…”

Section: Rbsn-5 Regulates Endocytosis In Drosophilamentioning

confidence: 99%

A novel function for the Rab5 effector Rabenosyn-5 in planar cell polarity

et al. 2010

View full text Add to dashboard Cite

SUMMARYIn addition to apicobasal polarization, some epithelia also display polarity within the plane of the epithelium. To what extent polarized endocytosis plays a role in the establishment and maintenance of planar cell polarity (PCP) is at present unclear. Here, we investigated the role of Rabenosyn-5 (Rbsn-5), an evolutionarily conserved effector of the small GTPase Rab5, in the development of Drosophila wing epithelium. We found that Rbsn-5 regulates endocytosis at the apical side of the wing epithelium and, surprisingly, further uncovered a novel function of this protein in PCP. At early stages of pupal wing development, the PCP protein Fmi redistributes between the cortex and Rab5-and Rbsn-5-positive early endosomes. During planar polarization, Rbsn-5 is recruited at the apical cell boundaries and redistributes along the proximodistal axis in an Fmidependent manner. At pre-hair formation, Rbsn-5 accumulates at the bottom of emerging hairs. Loss of Rbsn-5 causes intracellular accumulation of Fmi and typical PCP alterations such as defects in cell packing, in the polarized distribution of PCP proteins, and in hair orientation and formation. Our results suggest that establishment of planar polarity requires the activity of Rbsn-5 in regulating both the endocytic trafficking of Fmi at the apical cell boundaries and hair morphology.

show abstract

“…Similar to SARA, the FYVE domain protein-hepatic growth factor-regulated tyrosine kinase substrate (Hrs) has also been linking between the TGF-β/Smad signalling pathway and endosomal membrane trafficking (Raiborg et al, 2001b). Nevertheless, the endosomal targeting of Hrs is via a Rab5-independepent pathway (Raiborg et al, 2001a).…”

Section: Sara-and Rab5-mediated Early Endosome Enlargementmentioning

confidence: 99%

SARA, a FYVE domain protein, affects Rab5-mediated endocytosis

Chuang

et al. 2002

Journal of Cell Science

View full text Add to dashboard Cite

Rab5, a member of the small GTPase family of proteins, is primarily localized on early endosomes and has been proposed to participate in the regulation of early endosome trafficking. It has been reported that phosphatidylinositol 3-kinases and FYVE domain proteins, such as EEA1, can be recruited onto early endosomes and act as Rab5 effectors. SARA (Smad anchor for receptor activation), also a FYVE domain protein, was initially isolated as a participant in signal transduction from the transforming growth factorβ receptor. Overexpressed SARA has been found on EEA1-positive early endosomes. In this report, we show that endogenous SARA is present on early endosomes and overexpression of SARA causes endosomal enlargement. Functionally, SARA overexpression significantly delays the recycling of transferrin. The transferrin receptor distributed on the cell surfaces was also greatly reduced in cells overexpressing SARA. However, the internalization rate of transferrin is not affected by SARA overexpression. The morphological and functional alterations caused by SARA overexpression resemble those caused by overexpression of Rab5:GTP mutant Rab5Q79L. Finally,all SARA-mediated phenotypic changes can be counteracted by overexpression Rab5:GDP mutant Rab5S34N. These results collectively suggested that SARA plays an important functional role downstream of Rab5-regulated endosomal trafficking.

show abstract

Function of Hrs in endocytic trafficking and signalling

Cited by 47 publications

References 4 publications

Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains

Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains

A novel function for the Rab5 effector Rabenosyn-5 in planar cell polarity

SARA, a FYVE domain protein, affects Rab5-mediated endocytosis

Contact Info

Product

Resources

About