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Hedgehog signaling pathway

The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation.

Mammals have three Hedgehog homologues, Desert (DHH), Indian (IHH), and Sonic (SHH), of which Sonic is the best studied.[1] The pathway is equally important during vertebrate embryonic development and is therefore of interest in evolutionary developmental biology.

Protein patched homolog 1 (Ptch1) acts as receptor of Sonic Hedgehog protein (Shh) which is involved in formation of embryonic structures [2]. Embryogenesis is regulated by several pathways one of which is the Shh-Patch1-Gli all of which are highly conserved.

Mutations in Ptch1 are associated with holoprosencephaly[3].

High expression of Ptch1 messenger RNA indicates a risk of postresection recurrence of hepatocellular carcinoma[4].

. Ptch1 (residues 772-1023). . Ptch1 ectodomain 1 (colored in salmon) interacts with Shh as well as Ptch1 ectodomain 2 (colored in wheat) with . The Ptch1-Shh interaction is steroid-dependent and the 3D structure shows [5].

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Glycosylated human Ptch1 ectodomain 1 (salmon) complex with sonic hedgehog protein (deepskyblue), cholesterol derivative, Zn+2 (grey) and Ca+2 (green) ions (PDB code 6dmy)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993 Dec 31;75(7):1417-30. PMID:7916661
  2. ↑ Villavicencio EH, Walterhouse DO, Iannaccone PM. The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet. 2000 Nov;67(5):1047-54. doi: 10.1016/S0002-9297(07)62934-6. Epub , 2000 Sep 21. PMID:11001584 doi:http://dx.doi.org/10.1016/S0002-9297(07)62934-6
  3. ↑ Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M. Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. Hum Genet. 2002 Apr;110(4):297-301. doi: 10.1007/s00439-002-0695-5. Epub 2002 Mar, 2. PMID:11941477 doi:http://dx.doi.org/10.1007/s00439-002-0695-5
  4. ↑ Jeng KS, Sheen IS, Jeng WJ, Lin CC, Lin CK, Su JC, Yu MC, Fang HY. High expression of patched homolog-1 messenger RNA and glioma-associated oncogene-1 messenger RNA of sonic hedgehog signaling pathway indicates a risk of postresection recurrence of hepatocellular carcinoma. Ann Surg Oncol. 2013 Feb;20(2):464-73. doi: 10.1245/s10434-012-2593-y. Epub 2012 , Aug 22. PMID:22911366 doi:http://dx.doi.org/10.1245/s10434-012-2593-y
  5. ↑ Qian H, Cao P, Hu M, Gao S, Yan N, Gong X. Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm. Nat Commun. 2019 May 24;10(1):2320. doi: 10.1038/s41467-019-10234-9. PMID:31127104 doi:http://dx.doi.org/10.1038/s41467-019-10234-9

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