Cytoplasmic dynein intermediate-chain isoforms with different targeting properties created by tissue-specific alternative splicing.
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.
Department of Organismic & Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA. dnurmnsky@oeb.harvard.edu
D I
DI
Nurminsky
M V
MV
Nurminskaya
E V
EV
Benevolenskaya
Y Y
YY
Shevelyov
D L
DL
Hartl
V A
VA
Gvozdev
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins; D000072159:Dynactin Complex; D004398:Dyneins / Q000737:chemistry*; D005091:Exons / Q000235:genetics; D019476:Insect Proteins / Q000737:chemistry*; D007438:Introns / Q000235:genetics; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D000072159:Dynactin Complex; D019476:Insect Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C115375:sw protein, Drosophila; D004398:Dyneins