Myosin Va interacts with the exosomal protein spermine synthase

Author(s)

Dolce, Luciano G. ; Silva-Junior, Rui M. P. ; Assis, Leandro H. P. ; Nascimento, Andrey F. Z. ; Araujo, Jackeline S. ; Meschede, Ingrid P. ; Espreafico, Enilza M. ; de Giuseppe, Priscila O. ; Murakami, Mario T.

• Document type: Journal article
• Source: BIOSCIENCE REPORTS; v. 39, p. 11-pg., 2019-03-29.

Abstract

Myosin Va (MyoVa) is an actin-based molecular motor that plays key roles in the final stages of secretory pathways, including neurotransmitter release. Several studies have addressed how MyoVa coordinates the trafficking of secretory vesicles, but why this molecular motor is found in exosomes is still unclear. In this work, using a yeast two-hybrid screening system, we identified the direct interaction between the globular tail domain (GTD) of MyoVa and four protein components of exosomes: the WD repeat-containing protein 48 (WDR48), the cold shock domain-containing protein E1 (CSDE1), the tandem C2 domain-containing protein 1 (TC2N), and the enzyme spermine synthase (SMS). The interaction between the GTD of MyoVa and SMSwas further validated in vitro and displayed a Kd in the low micromolar range (3.5+-0.5 mu M). SMS localized together with MyoVa in cytoplasmic vesicles of breast cancer MCF-7 and neuroblastoma SH-SY5Y cell lines, known to produce exosomes. Moreover, MYO5A knockdown decreased the expression of SMS gene and rendered the distribution of SMS protein diffuse, supporting a role for MyoVa in SMS expression and targeting. (AU)

• FAPESP's process: 14/00584-5 - Understanding the role of phosphorylation cargo binding domain (CBD) in the regulation of unconventional myosins Class V
• Grantee: Luciano Graciani Dolce
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/04017-9 - Genomic and functional characterization of putative melanoma-restricted lncRNAs (RMELs)
• Grantee: Enilza Maria Espreafico
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/14257-8 - Structural studies of the globular domain of human myosin Va responsible for intracellular transport of organelles and vesicles
• Grantee: Andrey Fabricio Ziem Nascimento
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 14/03989-6 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS)
• Grantee: Margaret de Castro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/09720-9 - Studies of the role of phosphorylation and protein binding partners in regulating the function of human class V myosins
• Grantee: Mário Tyago Murakami
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/20229-7 - Human myosin-5A and the intracellular transport of cargoes: studies of the myosin-5A and adapter proteins complexes
• Grantee: Leandro Henrique de Paula Assis
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 16/10862-8 - Study of myosin-Va role in the processes of mitochondrial dynamics and mitophagy
• Grantee: Jackeline Souza Araújo
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC