The protein interactome of collapsin response mediator protein-2 (CRMP2/DPYSL2) reveals novel partner proteins in brain tissue

Autor(es)

Martins-de-Souza, Daniel ; Cassoli, Juliana S. ; Nascimento, Juliana M. ; Hensley, Kenneth ; Guest, Paul C. ; Pinzon-Velasco, Andres M. ; Turck, Christoph W.

• Tipo de documento: Artigo Científico
• Fonte: PROTEOMICS CLINICAL APPLICATIONS; v. 9, n. 9-10, p. 15-pg., 2015-10-01.

Resumo

Purpose: Collapsin response mediator protein-2 (CRMP2) is a CNS protein involved in neuronal development, axonal and neuronal growth, cell migration, and protein trafficking. Recent studies have linked perturbations in CRMP2 function to neurodegenerative disorders such as Alzheimer's disease, neuropathic pain, and Batten disease, and to psychiatric disorders such as schizophrenia. Like most proteins, CRMP2 functions though interactions with a molecular network of proteins and other molecules. Experimental design: Here, we have attempted to identify additional proteins of the CRMP2 interactome to provide further leads about its roles in neurological functions. We used a combined co-immunoprecipitation and shotgun proteomic approach in order to identify CRMP2 protein partners. Results: We identified 78 CRMP2 protein partners not previously reported in public protein interaction databases. These were involved in seven biological processes, which included cell signaling, growth, metabolism, trafficking, and immune function, according to Gene Ontology classifications. Furthermore, 32 different molecular functions were found to be associated with these proteins, such as RNA binding, ribosomal functions, transporter activity, receptor activity, serine/threonine phosphatase activity, cell adhesion, cytoskeletal protein binding and catalytic activity. In silico pathway interactome construction revealed a highly connected network with the most overrepresented functions corresponding to semaphorin interactions, along with axon guidance and WNT5A signaling. Conclusions and clinical relevance: Taken together, these findings suggest that the CRMP2 pathway is critical for regulating neuronal and synaptic architecture. Further studies along these lines might uncover novel biomarkers and drug targets for use in drug discovery. (AU)

• Processo FAPESP: 13/08711-3 - Desenvolvimento de um teste preditivo para medicação bem sucedida e compreensão das bases moleculares da esquizofrenia através da proteômica
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/25702-8 - Desenvolvimento de um teste preditivo para medicação bem sucedida e compreensão das bases moleculares da esquizofrenia através da proteômica
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 14/14881-1 - Compreensão da influência de componentes da via glicolítica na função dos oligodendrócitos: uma relação com os achados em esquizofrenia
• Beneficiário: Juliana Silva Cassoli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/10068-4 - EMU concedido no processo 13/08711-3: espectrômetro de massas Waters SYNAPT G2-Si HDMs + nanoACQUITY UPLC
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários