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Molecular and Cellular Biology, November 1998, p. 6816-6825, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Cytoplasmic Dynein Intermediate-Chain Isoforms with
Different Targeting Properties Created by Tissue-Specific
Alternative Splicing
Dmitry I.
Nurminsky,1,*
Maria V.
Nurminskaya,2
Elizaveta V.
Benevolenskaya,3,4
Yury Y.
Shevelyov,4
Daniel L.
Hartl,1 and
Vladimir
A.
Gvozdev4
Department of Organismic & Evolutionary
Biology, Harvard University, Cambridge, Massachusetts
021381;
Department of Anatomy and
Cell Biology, Tufts University School of Medicine, Boston,
Massachusetts 0211112;
University of
Missouri
Columbia, Columbia, Missouri
652113; and
Institute of Molecular
Genetics, Russian Academy of Sciences, Moscow 123182, Russia4
Received 13 April 1998/Returned for modification 5 June
1998/Accepted 14 August 1998
The intermediate chains (ICs) are the subunits of the cytoplasmic
dynein that provide binding of the complex to cargo organelles through
interaction of their N termini with dynactin. We present evidence that
in Drosophila, the IC subunits are represented by at least
10 structural isoforms, created by the alternative splicing of
transcripts from a unique Cdic gene. The splicing pattern
is tissue specific. A constitutive set of four IC
isoforms is expressed in all tissues tested; in addition,
tissue-specific isoforms are found in the ovaries and nervous tissue.
The structural variations between isoforms are limited to the N
terminus of the IC molecule, where the interaction with dynactin takes
place. This suggests differences in the dynactin-mediated organelle
binding by IC isoforms. Accordingly, when transiently expressed in
Drosophila Schneider-3 cells, the IC isoforms
differ in their intracellular targeting properties from each other. A
mechanism is proposed for the regulation of dynein binding to
organelles through the changes in the content of the IC isoform pool.
*
Corresponding author. Mailing address: Department of
Organismic & Evolutionary Biology, Harvard University, 16 Divinity
Ave., Cambridge, MA 02138. Phone: (617) 496-5540. Fax: (617) 496-5854. E-mail: dnurminsky{at}oeb.harvard.edu.
Molecular and Cellular Biology, November 1998, p. 6816-6825, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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