Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans

Autor(es):Mostrar menos -

Sobreira, Tiago J. P. ^[1] ; Marletaz, Ferdinand ^[2] ; Simoes-Costa, Marcos ^{[3, 4]} ; Schechtman, Deborah ^[5] ; Pereira, Alexandre C. ^[1] ; Brunet, Frederic ^[2] ; Sweeney, Sarah ^[6] ; Pani, Ariel ^{[7, 8]} ; Aronowicz, Jochanan ^[8] ; Lowe, Christopher J. ^[8] ; Davidson, Bradley ^[6] ; Laudet, Vincent ^[2] ; Bronner, Marianne ^[9] ; de Oliveira, Paulo S. L. ^[1] ; Schubert, Michael ^[2] ; Xavier-Neto, Jose ^[4]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Hosp Clin, Lab Genet & Cardiol Mol, Inst Coracao, BR-05403000 Sao Paulo - Brazil

^[2] Ecole Normale Super Lyon, Inst Genom Fonct Lyon, F-69364 Lyon 07 - France

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, BR-05508900 Sao Paulo - Brazil

^[4] Campus Lab Nacl Luz Sincrotron, Lab Nacl Biociencias, BR-13083970 Campinas, SP - Brazil

^[5] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508900 Sao Paulo - Brazil

^[6] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85724 - USA

^[7] Univ Chicago, Comm Evolutionary Biol, Chicago, IL 60637 - USA

^[8] Stanford Univ, Dept Biol, Hopkins Marine Stn, Pacific Grove, CA 93950 - USA

^[9] CALTECH, Div Biol 139 74, Pasadena, CA 91125 - USA

• Tipo de documento: Artigo Científico
• Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 108, n. 1, p. 226-231, JAN 4 2011.
• Citações Web of Science: 33

Resumo

Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification. (AU)

• Processo FAPESP: 06/50843-0 - Evolução e desenvolvimento das câmaras cardíacas
• Beneficiário: José Xavier Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular