The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 23 May 2006
doi: 10.1242/jcs.02978
Research Article
Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains
Camilla Raiborg,
Jørgen Wesche,
Lene Malerød,
and
Harald Stenmark*
* Author for correspondence (e-mail: stenmark{at}ulrik.uio.no)
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.
This article has been cited by other articles:
|
|
|
|
 
T. Falguieres, P.-P. Luyet, C. Bissig, C. C. Scott, M.-C. Velluz, and J. Gruenberg
In Vitro Budding of Intralumenal Vesicles into Late Endosomes Is Regulated by Alix and Tsg101
Mol. Biol. Cell,
November 1, 2008;
19(11):
4942 - 4955.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. I. Strochlic, B. C. Schmiedekamp, J. Lee, D. J. Katzmann, and C. G. Burd
Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome
Mol. Biol. Cell,
November 1, 2008;
19(11):
4694 - 4706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Craige, G. Salazar, and V. Faundez
Phosphatidylinositol-4-Kinase Type II Alpha Contains an AP-3-sorting Motif and a Kinase Domain That Are Both Required for Endosome Traffic
Mol. Biol. Cell,
April 1, 2008;
19(4):
1415 - 1426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Roxrud, C. Raiborg, N. M. Pedersen, E. Stang, and H. Stenmark
An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor
J. Cell Biol.,
March 24, 2008;
180(6):
1205 - 1218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Trajkovic, C. Hsu, S. Chiantia, L. Rajendran, D. Wenzel, F. Wieland, P. Schwille, B. Brugger, and M. Simons
Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes
Science,
February 29, 2008;
319(5867):
1244 - 1247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Hanyaloglu and M. von Zastrow
A Novel Sorting Sequence in the beta2-Adrenergic Receptor Switches Recycling from Default to the Hrs-dependent Mechanism
J. Biol. Chem.,
February 2, 2007;
282(5):
3095 - 3104.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2006
