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- Title
The Protein Kinase A Regulatory Subunit R1A (Prkar1a) Plays Critical Roles in Peripheral Nerve Development.
- Authors
Li Guo; Lee, Audrey A.; Rizvi, Tilat A.; Ratner, Nancy; Kirschner, Lawrence S.
- Abstract
Signaling through cAMP has been implicated in Schwann cell (SC) proliferation and myelination, but the signaling pathway components downstream of cAMP required for SC function remain unknown. Protein kinase A (PKA) is a potential downstream effector of cAMP. Here, we induced loss of Prkar1a, the gene encoding the type 1A regulatory subunit of PKA, in SC to study its role in nerve development; loss of Prkar1a is predicted to elevate PKA activity. Conditional Prkar1a knock-out in mouse SC (Prkar1a-SCKO) resulted in a dramatic and persistent axonal sorting defect, and unexpectedly decreased SC proliferation in Prkar1a-SCKO nerves in vivo. Effects were cell autonomous as they were recapitulated in vitro in Prkar1a-SCKO SC, which showed elevated PKA activity. In the few SCs sorted into 1:1 relationships with axons in vivo, SC myelination was premature in Prkar1a-SCKO nerves, correlating with global increase in the cAMPregulated transcription factor Oct-6 and expression of myelin basic protein. These data reveal a previously unknown role of PKA in axon sorting, an unexpected inhibitory role of PKA on SC cell proliferation in vivo and define the importance of Prkar1a in peripheral nerve development.
- Subjects
CYCLIC-AMP-dependent protein kinase; PERIPHERAL nervous system; MYELINATION; SCHWANN cells; CELL proliferation; LABORATORY mice
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 46, p17967
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0766-13.2013