The Kinesin-related Protein Costal2 Associates with Membranes in a Hedgehog-sensitive, Smoothened-independent Manner

Melanie A. Stegman, John A. Goetz, Manuel Ascano, Stacey K. Ogden, Kent E. Nybakken, David J Robbins

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

In Drosophila, Hedgehog (Hh) signal transduction has been shown to require a multiprotein complex (Hedgehog signaling complex (HSC)), which includes the Kinesin-related protein Costal2 (Cos2), the serine/threonine protein kinase Fused (Fu), and the transcription factor Cubitus interruptus (Ci). We present evidence that a biologically relevant fraction of the HSC is found in association with cellular membranes. We demonstrate that Cos2 is capable of tethering an exogenous protein to vesicular membranes and that Cos2 association with membranes is Hh-sensitive. In addition, we demonstrate that Cos2 associates with membranes in cells that lack the transmembrane protein Smoothened (Smo) through a domain of Cos2 distinct from its recently characterized Smo binding domain. We suggest that an Hh-regulated membrane binding activity of Cos2 is part of the mechanism by which Cos2 contributes to Hh signaling. We propose a model in which there are two distinct HSCs with discrete subcellular localizations and activities: one is endosome-associated and facilitates production of a repressor form of Ci (HSC-R), and one is Smo-associated and promotes Ci activation (HSC-A). In response to Hh and through interaction with Cos2, Smo mediates both inhibition of the endosome-associated HSC-R and activation of HSC-A at the plasma membrane.

Original languageEnglish
Pages (from-to)7064-7071
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number8
DOIs
StatePublished - Feb 20 2004
Externally publishedYes

Fingerprint

Kinesin
Hedgehogs
Membranes
Proteins
Chemical activation
Association reactions
Protein-Serine-Threonine Kinases
Endosomes
Multiprotein Complexes
Signal transduction
Cell membranes
Cell Membrane
Transcription Factors
Drosophila
Signal Transduction

ASJC Scopus subject areas

  • Biochemistry

Cite this

The Kinesin-related Protein Costal2 Associates with Membranes in a Hedgehog-sensitive, Smoothened-independent Manner. / Stegman, Melanie A.; Goetz, John A.; Ascano, Manuel; Ogden, Stacey K.; Nybakken, Kent E.; Robbins, David J.

In: Journal of Biological Chemistry, Vol. 279, No. 8, 20.02.2004, p. 7064-7071.

Research output: Contribution to journalArticle

Stegman, Melanie A. ; Goetz, John A. ; Ascano, Manuel ; Ogden, Stacey K. ; Nybakken, Kent E. ; Robbins, David J. / The Kinesin-related Protein Costal2 Associates with Membranes in a Hedgehog-sensitive, Smoothened-independent Manner. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 8. pp. 7064-7071.
@article{da06d995854c4da794d94aeecca38f5f,
title = "The Kinesin-related Protein Costal2 Associates with Membranes in a Hedgehog-sensitive, Smoothened-independent Manner",
abstract = "In Drosophila, Hedgehog (Hh) signal transduction has been shown to require a multiprotein complex (Hedgehog signaling complex (HSC)), which includes the Kinesin-related protein Costal2 (Cos2), the serine/threonine protein kinase Fused (Fu), and the transcription factor Cubitus interruptus (Ci). We present evidence that a biologically relevant fraction of the HSC is found in association with cellular membranes. We demonstrate that Cos2 is capable of tethering an exogenous protein to vesicular membranes and that Cos2 association with membranes is Hh-sensitive. In addition, we demonstrate that Cos2 associates with membranes in cells that lack the transmembrane protein Smoothened (Smo) through a domain of Cos2 distinct from its recently characterized Smo binding domain. We suggest that an Hh-regulated membrane binding activity of Cos2 is part of the mechanism by which Cos2 contributes to Hh signaling. We propose a model in which there are two distinct HSCs with discrete subcellular localizations and activities: one is endosome-associated and facilitates production of a repressor form of Ci (HSC-R), and one is Smo-associated and promotes Ci activation (HSC-A). In response to Hh and through interaction with Cos2, Smo mediates both inhibition of the endosome-associated HSC-R and activation of HSC-A at the plasma membrane.",
author = "Stegman, {Melanie A.} and Goetz, {John A.} and Manuel Ascano and Ogden, {Stacey K.} and Nybakken, {Kent E.} and Robbins, {David J}",
year = "2004",
month = "2",
day = "20",
doi = "10.1074/jbc.M311794200",
language = "English",
volume = "279",
pages = "7064--7071",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "8",

}

TY - JOUR

T1 - The Kinesin-related Protein Costal2 Associates with Membranes in a Hedgehog-sensitive, Smoothened-independent Manner

AU - Stegman, Melanie A.

AU - Goetz, John A.

AU - Ascano, Manuel

AU - Ogden, Stacey K.

AU - Nybakken, Kent E.

AU - Robbins, David J

PY - 2004/2/20

Y1 - 2004/2/20

N2 - In Drosophila, Hedgehog (Hh) signal transduction has been shown to require a multiprotein complex (Hedgehog signaling complex (HSC)), which includes the Kinesin-related protein Costal2 (Cos2), the serine/threonine protein kinase Fused (Fu), and the transcription factor Cubitus interruptus (Ci). We present evidence that a biologically relevant fraction of the HSC is found in association with cellular membranes. We demonstrate that Cos2 is capable of tethering an exogenous protein to vesicular membranes and that Cos2 association with membranes is Hh-sensitive. In addition, we demonstrate that Cos2 associates with membranes in cells that lack the transmembrane protein Smoothened (Smo) through a domain of Cos2 distinct from its recently characterized Smo binding domain. We suggest that an Hh-regulated membrane binding activity of Cos2 is part of the mechanism by which Cos2 contributes to Hh signaling. We propose a model in which there are two distinct HSCs with discrete subcellular localizations and activities: one is endosome-associated and facilitates production of a repressor form of Ci (HSC-R), and one is Smo-associated and promotes Ci activation (HSC-A). In response to Hh and through interaction with Cos2, Smo mediates both inhibition of the endosome-associated HSC-R and activation of HSC-A at the plasma membrane.

AB - In Drosophila, Hedgehog (Hh) signal transduction has been shown to require a multiprotein complex (Hedgehog signaling complex (HSC)), which includes the Kinesin-related protein Costal2 (Cos2), the serine/threonine protein kinase Fused (Fu), and the transcription factor Cubitus interruptus (Ci). We present evidence that a biologically relevant fraction of the HSC is found in association with cellular membranes. We demonstrate that Cos2 is capable of tethering an exogenous protein to vesicular membranes and that Cos2 association with membranes is Hh-sensitive. In addition, we demonstrate that Cos2 associates with membranes in cells that lack the transmembrane protein Smoothened (Smo) through a domain of Cos2 distinct from its recently characterized Smo binding domain. We suggest that an Hh-regulated membrane binding activity of Cos2 is part of the mechanism by which Cos2 contributes to Hh signaling. We propose a model in which there are two distinct HSCs with discrete subcellular localizations and activities: one is endosome-associated and facilitates production of a repressor form of Ci (HSC-R), and one is Smo-associated and promotes Ci activation (HSC-A). In response to Hh and through interaction with Cos2, Smo mediates both inhibition of the endosome-associated HSC-R and activation of HSC-A at the plasma membrane.

UR - http://www.scopus.com/inward/record.url?scp=1342282946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1342282946&partnerID=8YFLogxK

U2 - 10.1074/jbc.M311794200

DO - 10.1074/jbc.M311794200

M3 - Article

C2 - 14645371

AN - SCOPUS:1342282946

VL - 279

SP - 7064

EP - 7071

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 8

ER -