| Autor: |
Shane E. Tillo, Wei-Hong Xiong, Maho Takahashi, Sheng Miao, Adriana L. Andrade, Dale A. Fortin, Guang Yang, Maozhen Qin, Barbara F. Smoody, Philip J.S. Stork, Haining Zhong |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 19, Iss 3, Pp 617-629 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2017.03.070 |
| Popis: |
Summary: Protein kinase A (PKA) has diverse functions in neurons. At rest, the subcellular localization of PKA is controlled by A-kinase anchoring proteins (AKAPs). However, the dynamics of PKA upon activation remain poorly understood. Here, we report that elevation of cyclic AMP (cAMP) in neuronal dendrites causes a significant percentage of the PKA catalytic subunit (PKA-C) molecules to be released from the regulatory subunit (PKA-R). Liberated PKA-C becomes associated with the membrane via N-terminal myristoylation. This membrane association does not require the interaction between PKA-R and AKAPs. It slows the mobility of PKA-C and enriches kinase activity on the membrane. Membrane-residing PKA substrates are preferentially phosphorylated compared to cytosolic substrates. Finally, the myristoylation of PKA-C is critical for normal synaptic function and plasticity. We propose that activation-dependent association of PKA-C renders the membrane a unique PKA-signaling compartment. Constrained mobility of PKA-C may synergize with AKAP anchoring to determine specific PKA function in neurons. : The catalytic subunit of protein kinase A (PKA-C) is thought to remain in the cytosol when activated. Tillo et al. modify this view by showing that, upon activation in neurons, PKA-C becomes liberated from the regulatory subunit to associate with the membrane via myristoylation, where it preferentially phosphorylates membrane substrates. Keywords: cAMP-dependent kinase, PKA, myristoylation, activation-dependent membrane association, diffusion, mobility, synaptic plasticity, AMPA/NMDA current radio, mEPSC |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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