C-terminal Hh fragments are bound by lectins

Stable Identifier
R-HSA-5362437
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Promotion of the cholesterol-mediated autocleavage reaction is the only well documented role for the C-terminal region of intact Hh (reviewed in Briscoe and Therond, 2013), and recent in vitro studies suggest that the Hh-C fragment generated by autocleavage is subsequently targeted to the endoplasmic reticulum-associated degradation (ERAD) pathway (Chen et al, 2011; Huang et al, 2013). This pathway delivers N-glycosylated ER-resident substrates to a retrotranslocation channel, where they are ubiquitinated and translocated to the cytosol for proteasome-mediated degradation in an ATP-ase dependent fashion (reviewed in Vembar and Brodsky, 2008). Recognition and targettng of ER proteins for the ERAD pathway depends at least in part on modification and binding of the glycosyl groups. Consistent with this, depletion of the lectins OS9 and ERLEC1 abrogates degradation of the Hh-C fragments (Chen et al, 2011). OS9 and ERLEC1 may target Hh-C to the retrotranslocation channel by virtue of their interaction with SEL1, an ER membrane protein with established roles in the ERAD pathway (Christianson et al, 2008; Mueller et al, 2008; Hosokawa et al, 2008; Hosokawa et al, 2009).

Literature References
PubMed ID Title Journal Year
21357747 Processing and turnover of the Hedgehog protein in the endoplasmic reticulum

Chen, X, Tukachinsky, H, Huang, CH, Jao, C, Chu, YR, Tang, HY, Mueller, B, Schulman, S, Rapoport, TA, Salic, A

J. Cell Biol. 2011
19346256 Human OS-9, a lectin required for glycoprotein endoplasmic reticulum-associated degradation, recognizes mannose-trimmed N-glycans

Hosokawa, N, Kamiya, Y, Kamiya, D, Kato, K, Nagata, K

J. Biol. Chem. 2009
23867461 Derlin2 protein facilitates HRD1-mediated retro-translocation of sonic hedgehog at the endoplasmic reticulum

Huang, CH, Hsiao, HT, Chu, YR, Ye, Y, Chen, X

J. Biol. Chem. 2013
18711132 SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins

Mueller, B, Klemm, EJ, Spooner, E, Claessen, JH, Ploegh, HL

Proc. Natl. Acad. Sci. U.S.A. 2008
18502753 Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP

Hosokawa, N, Wada, I, Nagasawa, K, Moriyama, T, Okawa, K, Nagata, K

J. Biol. Chem. 2008
23719536 The mechanisms of Hedgehog signalling and its roles in development and disease

Briscoe, J, Thérond, PP

Nat. Rev. Mol. Cell Biol. 2013
19002207 One step at a time: endoplasmic reticulum-associated degradation

Vembar, SS, Brodsky, JL

Nat. Rev. Mol. Cell Biol. 2008
18264092 OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD

Christianson, JC, Shaler, TA, Tyler, RE, Kopito, RR

Nat. Cell Biol. 2008
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