N-HH binds to PTC receptor complex

Stable Identifier
R-DME-209178
Type
Reaction [binding]
Species
Drosophila melanogaster
Compartment
plasma membrane
ReviewStatus
5/5
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N-HH binds to PTC receptor complex
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N-HH bound to Dally-like protein (DLP) is presented to Patched (PTC) receptor and Induced Hedgehog/Brother of Induced Hedgehog (IHOG/BOI) co-receptor to form a ternary complex at the plasma membrane. N-HH binds directly to PTC. Binding is enhanced by the putative co-receptor, IHOG/BOI, which is a type I transmembrane protein that can bind N-HH directly in the presence of Heparin. Signal transduction is also enhanced by DLP, implying that heparan sulphate proteoglycan (HSPG)-associated N-HH may be the most potent form of Hedgehog. Binding of N-HH to PTC leads to PTC internalisation and lysosomal degradation, resulting in a reduction of extracellular N-HH levels and a relief of repression of Smoothened (SMO) by PTC, which depends on the opposing actions of free PTC and N-HH bound PTC.
Literature References
PubMed ID Title Journal Year
16041759 Mechanisms of Hedgehog gradient formation and interpretation

Torroja, C, Gorfinkiel, N, Guerrero, I

J Neurobiol 2005
8906787 The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog

Stone, DM, Hynes, M, Armanini, M, Swanson, TA, Gu, Q, Johnson, RL, Scott, MP, Pennica, D, Goddard, A, Phillips, H, Noll, M, Hooper, JE, de Sauvage, F, Rosenthal, A

Nature 1996
8898207 Dual roles for patched in sequestering and transducing Hedgehog

Chen, Y, Struhl, G

Cell 1996
16630821 The ihog cell-surface proteins bind Hedgehog and mediate pathway activation

Yao, S, Lum, L, Beachy, P

Cell 2006
8906794 Biochemical evidence that patched is the Hedgehog receptor

Marigo, V, Davey, RA, Zuo, Y, Cunningham, JM, Tabin, CJ

Nature 1996
17077139 Structure of a heparin-dependent complex of Hedgehog and Ihog

McLellan, JS, Yao, S, Zheng, X, Geisbrecht, BV, Ghirlando, R, Beachy, PA, Leahy, DJ

Proc Natl Acad Sci U S A 2006
15300262 Reading the Hedgehog morphogen gradient by measuring the ratio of bound to unbound Patched protein

Casali, A, Struhl, G

Nature 2004
15563523 Functions of heparan sulfate proteoglycans in cell signaling during development

Lin, X

Development 2004
12663920 Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells

Lum, L, Yao, S, Mozer, B, Rovescalli, A, Von Kessler, D, Nirenberg, M, Beachy, PA

Science 2003
15875013 Lipoprotein particles are required for Hedgehog and Wingless signalling

Panáková, D, Sprong, H, Marois, E, Thiele, C, Eaton, S

Nature 2005
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Authored
Williams, MG  (2006-12-07)
Reviewed
Kalderon, D  (2008-03-17)
Created
Williams, MG  (2006-12-08)
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