Nanoscale organization of hedgehog is essential for long-range signaling

Vyas, Neha ; Goswami, Debanjan ; Manonmani, A. ; Sharma, Pranav ; Ranganath, Hassan Annegowda ; VijayRaghavan, Krishnaswamy ; Shashidhara, L. S. ; Sowdhamini, Ramanathan ; Mayor, Satyajit (2008) Nanoscale organization of hedgehog is essential for long-range signaling Cell, 133 (7). pp. 1214-1227. ISSN 0092-8674

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/S00928...

Related URL: http://dx.doi.org/10.1016/j.cell.2008.05.026

Abstract

Hedgehog (Hh) plays crucial roles in tissue-patterning and activates signaling in Patched (Ptc)-expressing cells. Paracrine signaling requires release and transport over many cell diameters away by a process that requires interaction with heparan sulfate proteoglycans (HSPGs). Here, we examine the organization of functional, fluorescently tagged variants in living cells by using optical imaging, FRET microscopy, and mutational studies guided by bioinformatics prediction. We find that cell-surface Hh forms suboptical oligomers, further concentrated in visible clusters colocalized with HSPGs. Mutation of a conserved Lys in a predicted Hh-protomer interaction interface results in an autocrine signaling-competent Hh isoform incapable of forming dense nanoscale oligomers, interacting with HSPGs, or paracrine signaling. Thus, Hh exhibits a hierarchical organization from the nanoscale to visible clusters with distinct functions.

Item Type:Article
Source:Copyright of this article belongs to Cell Press Inc.
ID Code:26687
Deposited On:08 Dec 2010 13:23
Last Modified:17 May 2016 09:59

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