Reactome | C-terminal Hh fragments are bound by lectins

C-terminal Hh fragments are bound by lectins

Stable Identifier

R-HSA-5362437

Type

Reaction [binding]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

C-terminal Hh fragments are bound by lectins

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
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
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
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