Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9).

M. Venoux (1) , K. Delmouly (1) , Ollivier Milhavet (1) , S. Vidal-Eychenié (1) , D. Giorgi (1) , Sylvie Rouquier (1)

1 IGH - Institut de génétique humaine

Background : ASAP is a newly characterized microtubule-associated protein (MAP) essential for propercell-cycling. We have previously shown that expression deregulation of human ASAP results in profounddefects in mitotic spindle formation and mitotic progression leading to aneuploidy, cytokinesis defects and/or cell death. In the present work we analyze the structure and evolution of the ASAP gene, as well as thedomain composition of the encoded protein. Mouse and Xenopus cDNAs were cloned, the tissueexpression characterized and the overexpression profile analyzed. Results : Bona fide ASAP orthologs are found in vertebrates with more distantly related potentialorthologs in invertebrates. This single-copy gene is conserved in mammals where it maps to syntenicchromosomal regions, but is also clearly identified in bird, fish and frog. The human gene is stronglyexpressed in brain and testis as a 2.6 Kb transcript encoding a ~110 KDa protein. The protein containsMAP, MIT-like and THY domains in the C-terminal part indicative of microtubule interaction, while the N-terminal part is more divergent. ASAP is composed of ~42% alpha helical structures, and two main coiled-coil regions have been identified. Different sequence features may suggest a role in DNA damage response. As with human ASAP, the mouse and Xenopus proteins localize to the microtubule network in interphaseand to the mitotic spindle during mitosis. Overexpression of the mouse protein induces mitotic defectssimilar to those observed in human. In situ hybridization in testis localized ASAP to the germ cells, whereasin culture neurons ASAP localized to the cell body and growing neurites. Conclusion : The conservation of ASAP indicated in our results reflects an essential function invertebrates. We have cloned the ASAP orthologs in mouse and Xenopus, two valuable models to studythe function of ASAP. Tissue expression of ASAP revealed a high expression in brain and testis, two tissuesrich in microtubules. ASAP associates to the mitotic spindle and cytoplasmic microtubules, and representsa key factor of mitosis with possible involvement in other cell cycle processes. It may have a role inspermatogenesis and also represents a potential new target for antitumoral drugs. Possible involvement inneuron dynamics also highlights ASAP as a candidate target in neurodegenerative diseases

Domaines: Génétique

M. Venoux, K. Delmouly, Ollivier Milhavet, S. Vidal-Eychenié, D. Giorgi, et al.. Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9).. BMC Genomics, 2008, 9 (1), pp.406. ⟨10.1186/1471-2164-9-406⟩. ⟨hal-00322423⟩