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Unveiling the interaction between the molecular motor Myosin Vc and the small GTPase Rab3A

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Autor(es):
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Dolce, Luciano G. [1, 2] ; Ohbayashi, Norihiko [3, 4, 5] ; da Silva, Daniel F. C. [6] ; Ferrari, Allan J. R. [7] ; Pirolla, Renan A. S. [7, 6] ; Schwarzer, Ana C. de A. P. [1] ; Zanphorlin, Leticia M. [6] ; Cabral, Lucelia [6] ; Fioramonte, Mariana [7] ; Ramos, Carlos H. I. [8] ; Gozzo, Fabio Cesar [7] ; Fukuda, Mitsunori [3] ; de Giuseppe, Priscila O. [1, 6] ; Murakami, Mario T. [1, 6]
Número total de Autores: 14
Afiliação do(s) autor(es):
[1] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083100 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Inst Biol, Grad Program Funct & Mol Biol, Campinas, SP - Brazil
[3] Tohoku Univ, Grad Sch Life Sci, Dept Integrat Life Sci, Lab Membrane Trafficking Mech, Aoba Ku, Sendai, Miyagi 9808578 - Japan
[4] Univ Tsukuba, Fac Med, Dept Physiol Chem, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575 - Japan
[5] Univ Tsukuba, Grad Sch Comprehens Human Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575 - Japan
[6] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biorenewables Natl Lab LNBR, BR-13083100 Campinas, SP - Brazil
[7] Univ Estadual Campinas, Inst Chem, Dalton Mass Spectrometry Lab, BR-13083970 Campinas, SP - Brazil
[8] Univ Estadual Campinas, Inst Chem, BR-13083970 Campinas, SP - Brazil
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF PROTEOMICS; v. 212, FEB 10 2020.
Citações Web of Science: 0
Resumo

Vertebrates usually have three class V myosin paralogues (MyoV) to control membrane trafficking in the actin rich cell cortex, but their functional overlapping or differentiation through cargoes selectivity is yet only partially understood. In this work, we reveal that the globular tail domain of MyoVc binds to the active form of small GTPase Rab3A with nanomolar affinity, a feature shared with MyoVa but not with MyoVb. Using molecular docking analyses guided by chemical cross-linking restraints, we propose a model to explain how Rab3A selectively recognizes MyoVa and MyoVc via a distinct binding site from that used by Rab11A. The MyoVa/c binding interface involves multiple residues from both lobules (I and II) and the short helix at the alpha 2-alpha 3 link region, which is conserved between MyoVa and MyoVc, but not in MyoVb. This motif is also responsible for the selective binding of RILPL2 by MyoVa and potentially MyoVc. Together, these findings support the selective recruitment of MyoVa and MyoVc to exocytic pathways via Rab3A and expand our knowledge about the functional evolution of class V myosins. Significance: Hormone secretion, neurotransmitter release, and cytoplasm membrane recycling are examples of processes that rely on the interaction of molecular motors and Rab GTPases to regulate the intracellular trafficking and tethering of vesicles. Defects in these proteins may cause neurological impairment, immunodeficiency, and other severe disorders, being fatal in some cases. Despite their crucial roles, little is known about how these molecular motors are selectively recruited by specific members of the large family of Rab GTPases. In this study, we unveil the interaction between the actin-based molecular motor Myosin Vc and the small GTPase Rab3A, a key coordinator of vesicle trafficking and exocytosis in mammalian cells. Moreover, we propose a model for their recognition and demonstrate that Rab3A specifically binds to the globular tail of Myosins Va and Vc, but not of Myosin Vb, advancing our knowledge about the molecular basis for the selective recruitment of class V myosins by Rab GTPases. (AU)

Processo FAPESP: 14/09720-9 - Estudos do papel da fosforilação e da ligação de proteínas parceiras na regulação da função de miosinas V humanas
Beneficiário:Mário Tyago Murakami
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/13195-2 - Modelagem da estrutura de proteínas e de complexos protéicos usando dados de espectrometria de massas
Beneficiário:Allan Jhonathan Ramos Ferrari
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 14/00584-5 - Entendimento do papel da fosforilação do domínio de ligação a cargas (CBD) na regulação da função de miosinas não convencionais da Classe V
Beneficiário:Luciano Graciani Dolce
Linha de fomento: Bolsas no Brasil - Doutorado Direto