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


METHODS
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
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.
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.|UNICAMP's Neurobiology Center, Campinas, Brazil.
Daniel
D
Martins-de-Souza
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Juliana S
JS
Cassoli
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.|D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
Juliana M
JM
Nascimento
Department of Pathology, University of Toledo, Toledo, OH, USA.|Department of Neurosciences, University of Toledo, Toledo, OH, USA.
Kenneth
K
Hensley
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Paul C
PC
Guest
Bioinformatics and Computational Systems Biology Group, Institute for Genetics, National University of Colombia, Bogotá, Colombia.
Andres M
AM
Pinzon-Velasco
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Christoph W
CW
Turck
D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D012559:Schizophrenia / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2
Collapsin response mediator protein 2 (CRMP2); Dihydropyrimidinase-related protein 2 (DPYSL2); Interactome; MS; Schizophrenia