Mitochondrial localization of CNP2 is regulated by phosphorylation of the N-terminal targeting signal by PKC: implications of a mitochondrial function for CNP2 in glial and non-glial cells

John Lee; Ryan C O'Neill; Min Woo Park; Michel Gravel; Peter E Braun

doi:10.1016/j.mcn.2005.10.017

Mitochondrial localization of CNP2 is regulated by phosphorylation of the N-terminal targeting signal by PKC: implications of a mitochondrial function for CNP2 in glial and non-glial cells

Mol Cell Neurosci. 2006 Mar;31(3):446-62. doi: 10.1016/j.mcn.2005.10.017. Epub 2005 Dec 15.

Authors

John Lee¹, Ryan C O'Neill, Min Woo Park, Michel Gravel, Peter E Braun

Affiliation

¹ Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6. johnlee@gene.com

PMID: 16343930
DOI: 10.1016/j.mcn.2005.10.017

Abstract

Both 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNP) isoforms are abundantly expressed in myelinating cells. CNP2 differs from CNP1 by a 20 amino acid N-terminal extension and is also expressed at much lower levels in non-myelinating tissues. The functional role of CNP2, apart from CNP1, and the significance for CNP2 expression in non-myelinating tissues are unknown. Here, we demonstrate that CNP2 is translocated to mitochondria by virtue of a mitochondrial targeting signal at the N-terminus. PKC-mediated phosphorylation of the targeting signal inhibits CNP2 translocation to mitochondria, thus retaining it in the cytoplasm. CNP2 is imported into mitochondria and the targeting signal cleaved, yielding a mature, truncated form similar in size to CNP1. CNP2 is entirely processed in adult liver and embryonic brain, indicating that it is localized specifically to mitochondria in non-myelinating cells. Our results point to a broader biological role for CNP2 in mitochondria that is likely to be different from its specific role in the cytoplasm, along with CNP1, during myelination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
Animals
Brain / embryology
Brain / enzymology*
Brain / ultrastructure
Cell Respiration / physiology
Cyclic AMP-Dependent Protein Kinases / metabolism
Energy Metabolism / physiology
Green Fluorescent Proteins
HeLa Cells
Hepatocytes / enzymology
Hepatocytes / ultrastructure
Humans
Immunohistochemistry
Liver / enzymology
Liver / ultrastructure
Microscopy, Electron, Transmission
Mitochondria / enzymology*
Mitochondria / ultrastructure
Neuroglia / enzymology*
Neuroglia / ultrastructure
Neurons / enzymology*
Neurons / ultrastructure
Phosphoric Diester Hydrolases / genetics
Phosphoric Diester Hydrolases / metabolism*
Phosphorylation
Protein Kinase C / chemistry
Protein Kinase C / metabolism*
Protein Structure, Tertiary / physiology
Protein Transport / physiology
Rats
Subcellular Fractions
Transfection

Substances

Green Fluorescent Proteins
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Phosphoric Diester Hydrolases
2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
CNP protein, human
Cnp protein, rat