Interaction between LIS1 and doublecortin, two lissencephaly gene products

Citation
M. Caspi et al., Interaction between LIS1 and doublecortin, two lissencephaly gene products, HUM MOL GEN, 9(15), 2000, pp. 2205-2213
Citations number
32
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN MOLECULAR GENETICS
ISSN journal
09646906 → ACNP
Volume
9
Issue
15
Year of publication
2000
Pages
2205 - 2213
Database
ISI
SICI code
0964-6906(20000922)9:15<2205:IBLADT>2.0.ZU;2-G
Abstract
Mutations in either LIS1 or DCX are the most common cause for type I lissen cephaly. Here we report that LIS1 and DCX interact physically both in vitro and in vivo. Epitope-tagged DCX transiently expressed in COS cells can be co-immunoprecipitated with endogenous LIS1, Furthermore, endogenous DCX cou ld be co-immunoprecipitated with endogenous LIS1 in embryonic brain extract s, demonstrating an in vivo association. The two protein products also co-l ocalize in transfected cells and in primary neuronal cells. In addition, we demonstrate homodimerization of DCX in vitro, Using fragments of both LIS1 and DCX, the domains of interaction were mapped. LIS1 and DCX interact wit h tubulin and microtubules. Our results suggest that addition of DCX and LI S1 to tubulin enhances polymerization in an additive fashion. In in vitro c ompetition assays, when LIS1 is added first, DCX competes with LIS1 in its binding to microtubules, but when DCX is added prior to the addition of LIS 1 it enhances the binding of LIS1 to microtubules. We conclude that LIS1 an d DCX cross-talk is important to microtubule function in the developing cer ebral cortex.