Identification of a family of fatty-acid-speciated sonic hedgehog proteins, whose members display differential biological properties

Jun Long, Robert Tokhunts, William M. Old, Stephane Houel, Jezabel Rodgriguez-Blanco, Samer Singh, Neal Schilling, Anthony J Capobianco, Natalie G. Ahn, David J Robbins

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Hedgehog (HH) proteins are proteolytically processed into a biologically active form that is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is overexpressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels and showed that it was more potent than SHH isolated from overexpressing cells. Furthermore, the SHH in our preparations was modified with a diverse spectrum of fatty acids on its amino termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH affected its trafficking to lipid rafts as well as its potency. Our results suggest that HH proteins exist as a family of diverse lipid-speciated proteins that might be altered in different physiological and pathological contexts in order to regulate distinct properties of HH proteins.

Original languageEnglish (US)
Pages (from-to)1280-1287
Number of pages8
JournalCell Reports
Volume10
Issue number8
DOIs
StatePublished - Mar 3 2015

Fingerprint

Hedgehog Proteins
Fatty Acids
Lipids
Palmitates
Proteins
Cholesterol
Cells
Chemical analysis
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Identification of a family of fatty-acid-speciated sonic hedgehog proteins, whose members display differential biological properties. / Long, Jun; Tokhunts, Robert; Old, William M.; Houel, Stephane; Rodgriguez-Blanco, Jezabel; Singh, Samer; Schilling, Neal; Capobianco, Anthony J; Ahn, Natalie G.; Robbins, David J.

In: Cell Reports, Vol. 10, No. 8, 03.03.2015, p. 1280-1287.

Research output: Contribution to journalArticle

Long, Jun ; Tokhunts, Robert ; Old, William M. ; Houel, Stephane ; Rodgriguez-Blanco, Jezabel ; Singh, Samer ; Schilling, Neal ; Capobianco, Anthony J ; Ahn, Natalie G. ; Robbins, David J. / Identification of a family of fatty-acid-speciated sonic hedgehog proteins, whose members display differential biological properties. In: Cell Reports. 2015 ; Vol. 10, No. 8. pp. 1280-1287.
@article{87e3541b0df34fd6849c3d8eec502ae7,
title = "Identification of a family of fatty-acid-speciated sonic hedgehog proteins, whose members display differential biological properties",
abstract = "Hedgehog (HH) proteins are proteolytically processed into a biologically active form that is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is overexpressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels and showed that it was more potent than SHH isolated from overexpressing cells. Furthermore, the SHH in our preparations was modified with a diverse spectrum of fatty acids on its amino termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH affected its trafficking to lipid rafts as well as its potency. Our results suggest that HH proteins exist as a family of diverse lipid-speciated proteins that might be altered in different physiological and pathological contexts in order to regulate distinct properties of HH proteins.",
author = "Jun Long and Robert Tokhunts and Old, {William M.} and Stephane Houel and Jezabel Rodgriguez-Blanco and Samer Singh and Neal Schilling and Capobianco, {Anthony J} and Ahn, {Natalie G.} and Robbins, {David J}",
year = "2015",
month = "3",
day = "3",
doi = "10.1016/j.celrep.2015.01.058",
language = "English (US)",
volume = "10",
pages = "1280--1287",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",

}

TY - JOUR

T1 - Identification of a family of fatty-acid-speciated sonic hedgehog proteins, whose members display differential biological properties

AU - Long, Jun

AU - Tokhunts, Robert

AU - Old, William M.

AU - Houel, Stephane

AU - Rodgriguez-Blanco, Jezabel

AU - Singh, Samer

AU - Schilling, Neal

AU - Capobianco, Anthony J

AU - Ahn, Natalie G.

AU - Robbins, David J

PY - 2015/3/3

Y1 - 2015/3/3

N2 - Hedgehog (HH) proteins are proteolytically processed into a biologically active form that is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is overexpressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels and showed that it was more potent than SHH isolated from overexpressing cells. Furthermore, the SHH in our preparations was modified with a diverse spectrum of fatty acids on its amino termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH affected its trafficking to lipid rafts as well as its potency. Our results suggest that HH proteins exist as a family of diverse lipid-speciated proteins that might be altered in different physiological and pathological contexts in order to regulate distinct properties of HH proteins.

AB - Hedgehog (HH) proteins are proteolytically processed into a biologically active form that is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is overexpressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels and showed that it was more potent than SHH isolated from overexpressing cells. Furthermore, the SHH in our preparations was modified with a diverse spectrum of fatty acids on its amino termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH affected its trafficking to lipid rafts as well as its potency. Our results suggest that HH proteins exist as a family of diverse lipid-speciated proteins that might be altered in different physiological and pathological contexts in order to regulate distinct properties of HH proteins.

UR - http://www.scopus.com/inward/record.url?scp=84924541736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924541736&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.01.058

DO - 10.1016/j.celrep.2015.01.058

M3 - Article

C2 - 25732819

AN - SCOPUS:84924541736

VL - 10

SP - 1280

EP - 1287

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 8

ER -