Nanoscale organization of hedgehog is essential for long-range signaling

Neha Vyas and Goswami, Debanjan and Manonmani, A. and Sharma, Pranav and Ranganath, H. A. and Vijay Raghavan, K. and Shashidhara, L. S. and Sowdhamini, R. and Mayor, Satyajit (2008) Nanoscale organization of hedgehog is essential for long-range signaling. Cell, 133 (7). 1214 - 1227. ISSN 1097-4172

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Summary 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
Uncontrolled Keywords: CELLBIO
Subjects: B Life Science > Zoology
Divisions: Department of > Zoology
Depositing User: Manjula P Library Assistant
Date Deposited: 28 Aug 2019 10:23
Last Modified: 30 Jun 2020 10:15

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