HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 40, 41537-41545, October 1, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/40/41537    most recent M406601200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nielsen, A. L. Articles by Jørgensen, A. L. Search for Related Content PubMed PubMed Citation Articles by Nielsen, A. L. Articles by Jørgensen, A. L. Social Bookmarking                      What's this?

Self-assembly of the Cytoskeletal Glial Fibrillary Acidic Protein Is Inhibited by an Isoform-specific C Terminus^*

Anders Lade Nielsen and Arne Lund Jørgensen

From the Department of Human Genetics, Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark

The predominant isoform of glial fibrillary acidic protein (GFAP), GFAP, is the characteristic building block of the cytoskeletal intermediate filaments in astrocytes. Isoform GFAP, produced by alternative splicing of the GFAP gene, includes a new tail domain that confers a presenilin binding capacity. We here show that the GFAP tail prevents GFAP homodimerization and homomeric filament formation, whereas the ability to form heterodimers and filaments with GFAP is retained. Furthermore, GFAP shows decreased affinity for several GFAP-interacting proteins. A GFAP tail mutation that results in gain of GFAP dimerization and filament formation abolishes presenilin binding. This mutation also abolishes interaction between the tail and the coiled-coil domain of GFAP. Together, this indicates that direct interaction between the coiled-coil and tail domains may serve as an inhibitory mechanism for homomeric dimerization and filament formation. We propose that the GFAP isoform represents a new functionally distinct component of GFAP intermediate filaments.

Received for publication, June 14, 2004

^* This work was supported by the Danish Research Councils SJVF and SSVF (Storre Tvaerfaglige Forskergrupper (STF) program), the Danish Cancer Society, and the Novo Nordic Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 45-89421685; Fax: 45-86123173; E-mail: aln{at}humgen.au.dk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M.-D. Perng, S.-F. Wen, T. Gibbon, J. Middeldorp, J. Sluijs, E. M. Hol, and R. A. Quinlan Glial Fibrillary Acidic Protein Filaments Can Tolerate the Incorporation of Assembly-compromised GFAP-{delta}, but with Consequences for Filament Organization and {alpha}B-Crystallin Association Mol. Biol. Cell, October 1, 2008; 19(10): 4521 - 4533. [Abstract] [Full Text] [PDF]

				J. Blechingberg, S. Lykke-Andersen, T. H. Jensen, A. L. Jorgensen, and A. L. Nielsen Regulatory mechanisms for 3'-end alternative splicing and polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, transcript Nucleic Acids Res., December 3, 2007; 35(22): 7636 - 7650. [Abstract] [Full Text] [PDF]

				J.-H. F. Peng, F.-T. Kung, W. Peng, and J. C. Parker Jr Increased ALZ-50 Immunoreactivity in CSF of Pseudotumor Cerebri Patients. Ann. Clin. Lab. Sci., March 1, 2006; 36(2): 151 - 156. [Abstract] [Full Text] [PDF]