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

<p>Abstract</p> <p>Background</p> <p>ASAP is a newly characterized microtubule-associated protein (MAP) essential for proper cell-cycling. We have previously shown that expression deregulation of human ASAP results in profound defects in mitotic spindle formation and mi...

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Main Authors: Giorgi Dominique, Vidal-Eychenié Sophie, Milhavet Ollivier, Delmouly Karine, Venoux Magali, Rouquier Sylvie
Format: Article
Language:English
Published: BMC 2008-09-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/9/406
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spelling doaj-ca2d57303109411abd48fae17f5fdc122020-11-24T22:00:04ZengBMCBMC Genomics1471-21642008-09-019140610.1186/1471-2164-9-406Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9)Giorgi DominiqueVidal-Eychenié SophieMilhavet OllivierDelmouly KarineVenoux MagaliRouquier Sylvie<p>Abstract</p> <p>Background</p> <p>ASAP is a newly characterized microtubule-associated protein (MAP) essential for proper cell-cycling. We have previously shown that expression deregulation of human ASAP results in profound defects 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 the domain composition of the encoded protein. Mouse and <it>Xenopus </it>cDNAs were cloned, the tissue expression characterized and the overexpression profile analyzed.</p> <p>Results</p> <p><it>Bona fide </it>ASAP orthologs are found in vertebrates with more distantly related potential orthologs in invertebrates. This single-copy gene is conserved in mammals where it maps to syntenic chromosomal regions, but is also clearly identified in bird, fish and frog. The human gene is strongly expressed in brain and testis as a 2.6 Kb transcript encoding a ~110 KDa protein. The protein contains MAP, 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 <it>Xenopus </it>proteins localize to the microtubule network in interphase and to the mitotic spindle during mitosis. Overexpression of the mouse protein induces mitotic defects similar to those observed in human. <it>In situ </it>hybridization in testis localized ASAP to the germ cells, whereas in culture neurons ASAP localized to the cell body and growing neurites.</p> <p>Conclusion</p> <p>The conservation of ASAP indicated in our results reflects an essential function in vertebrates. We have cloned the ASAP orthologs in mouse and <it>Xenopus</it>, two valuable models to study the function of ASAP. Tissue expression of ASAP revealed a high expression in brain and testis, two tissues rich in microtubules. ASAP associates to the mitotic spindle and cytoplasmic microtubules, and represents a key factor of mitosis with possible involvement in other cell cycle processes. It may have a role in spermatogenesis and also represents a potential new target for antitumoral drugs. Possible involvement in neuron dynamics also highlights ASAP as a candidate target in neurodegenerative diseases.</p> http://www.biomedcentral.com/1471-2164/9/406
collection DOAJ
language English
format Article
sources DOAJ
author Giorgi Dominique
Vidal-Eychenié Sophie
Milhavet Ollivier
Delmouly Karine
Venoux Magali
Rouquier Sylvie
spellingShingle Giorgi Dominique
Vidal-Eychenié Sophie
Milhavet Ollivier
Delmouly Karine
Venoux Magali
Rouquier Sylvie
Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9)
BMC Genomics
author_facet Giorgi Dominique
Vidal-Eychenié Sophie
Milhavet Ollivier
Delmouly Karine
Venoux Magali
Rouquier Sylvie
author_sort Giorgi Dominique
title Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9)
title_short Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9)
title_full Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9)
title_fullStr Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9)
title_full_unstemmed Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9)
title_sort gene organization, evolution and expression of the microtubule-associated protein asap (map9)
publisher BMC
series BMC Genomics
issn 1471-2164
publishDate 2008-09-01
description <p>Abstract</p> <p>Background</p> <p>ASAP is a newly characterized microtubule-associated protein (MAP) essential for proper cell-cycling. We have previously shown that expression deregulation of human ASAP results in profound defects 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 the domain composition of the encoded protein. Mouse and <it>Xenopus </it>cDNAs were cloned, the tissue expression characterized and the overexpression profile analyzed.</p> <p>Results</p> <p><it>Bona fide </it>ASAP orthologs are found in vertebrates with more distantly related potential orthologs in invertebrates. This single-copy gene is conserved in mammals where it maps to syntenic chromosomal regions, but is also clearly identified in bird, fish and frog. The human gene is strongly expressed in brain and testis as a 2.6 Kb transcript encoding a ~110 KDa protein. The protein contains MAP, 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 <it>Xenopus </it>proteins localize to the microtubule network in interphase and to the mitotic spindle during mitosis. Overexpression of the mouse protein induces mitotic defects similar to those observed in human. <it>In situ </it>hybridization in testis localized ASAP to the germ cells, whereas in culture neurons ASAP localized to the cell body and growing neurites.</p> <p>Conclusion</p> <p>The conservation of ASAP indicated in our results reflects an essential function in vertebrates. We have cloned the ASAP orthologs in mouse and <it>Xenopus</it>, two valuable models to study the function of ASAP. Tissue expression of ASAP revealed a high expression in brain and testis, two tissues rich in microtubules. ASAP associates to the mitotic spindle and cytoplasmic microtubules, and represents a key factor of mitosis with possible involvement in other cell cycle processes. It may have a role in spermatogenesis and also represents a potential new target for antitumoral drugs. Possible involvement in neuron dynamics also highlights ASAP as a candidate target in neurodegenerative diseases.</p>
url http://www.biomedcentral.com/1471-2164/9/406
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