title: Copine1 C2 domains have a critical calcium-independent role in the neuronal differentiation of hippocampal progenitor HiB5 cells.
abstract: Copine1 (CPNE1) has tandem C2 domains and an A domain and is known as a calcium-dependent membrane-binding protein that regulates signal transduction and membrane trafficking. We previously demonstrated that CPNE1 directly induces neuronal differentiation via Akt phosphorylation in the hippocampal progenitor cell line, HiB5. To determine which region of CPNE1 is related to HiB5 cell neurite outgrowth, we constructed several mutants. Our results show that over-expression of each C2 domain of CPNE1 increased neurite outgrowth and expression of the neuronal marker protein neurofilament (NF). Even though protein localization of the calcium binding-deficient mutant of CPNE1 was not affected by ionomycin, this mutant increased neurite outgrowth and NF expression in HiB5 cells. Furthermore, Akt phosphorylation was increased by over-expression of the calcium binding-deficient CPNE1 mutant. These results suggest that neither cellular calcium levels nor the localization of CPNE1 affect its function in neuronal differentiation. Collectively, our findings indicating that the C2 domains of CPNE1 play a calcium-independent role in regulating the neuronal differentiation of HiB5 cells.
authors.affiliation: Department of Physiology, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Nammi
authors.initials: N
authors.lastname: Park
authors.affiliation: Department of Physiology, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jae Cheal
authors.initials: JC
authors.lastname: Yoo
authors.affiliation: Department of Physiology, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Radiology, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Seong-Geun
authors.initials: SG
authors.lastname: Hong
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 136-703, Republic of Korea. Electronic address: jaeyong68@korea.ac.kr.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D017384:Sequence Deletion; D015398:Signal Transduction
chemical_list: C000597435:CPNE1 protein, rat; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D050505:Mutant Proteins; D002118:Calcium
keywords: Akt; C2 domain; Copine1; HiB5 cell; NF; Neuronal differentiation