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Nanoscale Organization of Hedgehog Is Essential for Long-Range Signaling

Mayor, S and Sowdhamini, R. A. and Shashidhara, L. S. C. and VijayRaghavan, K. A. and Ranganath, H. A. B. and Sharma, P. A. and Manonmani, A. A. and Goswami, D. A. and Vyas, N. A. B. (2008) Nanoscale Organization of Hedgehog Is Essential for Long-Range Signaling. cell . pp. 1214-1227.

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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. © 2008 Elsevier Inc. All rights reserved.

Item Type:Article
Subjects:Biomedical Science > Nanobiotechnology
Divisions:Faculty of Medicine, Health and Life Sciences > School of Biological Sciences
ID Code:3938
Deposited By:JNCASR
Deposited On:03 Feb 2009 04:21
Last Modified:12 Feb 2009 11:48

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