Protein phosphatase-1M and Rho-kinase affect exocytosis from cortical synaptosomes and influence neurotransmission at a glutamatergic giant synapse of the rat auditory system

Beáta Lontay, Balázs Pál, Zoltán Serfz, Áron Kszeghy, Géza Szücs, Zoltán Rusznák, Ferenc Erdodi

Research output: Article

6 Citations (Scopus)

Abstract

Protein phosphatase-1M (PP1M, myosin phosphatase) consists of a PP1 catalytic subunit (PP1c) and the myosin phosphatase target subunit-1 (MYPT1). RhoA-activated kinase (ROK) regulates PP1M via inhibitory phosphorylation of MYPT1. Using multidisciplinary approaches, we have studied the roles of PP1M and ROK in neurotransmission. Electron microscopy demonstrated the presence of MYPT1 and ROK in both pre- and post-synaptic terminals. Tautomycetin (TMC), a PP1-specific inhibitor, decreased the depolarization-induced exocytosis from cortical synaptosomes. trans-4-[(1R)-1-aminoethyl]-N-4- pyridinylcyclohexanecarboxamide dihydrochloride, a ROK-specific inhibitor, had the opposite effect. Mass spectrometry analysis identified several MYPT1-bound synaptosomal proteins, of which interactions of synapsin-I, syntaxin-1, calcineurin-A subunit, and Ca2+/calmodulin-dependent kinase II with MYPT1 were confirmed. In intact synaptosomes, TMC increased, whereas Y27632 decreased the phosphorylation levels of MYPT1Thr696, myosin-II light chainSer19, synapsin-ISer9, and syntaxin-1 Ser14, indicating that PP1M and ROK influence their phosphorylation status. Confocal microscopy indicated that MYPT1 and ROK are present in the rat ventral cochlear nucleus both pre- and post-synaptically. Analysis of the neurotransmission in an auditory glutamatergic giant synapse demonstrated that PP1M and ROK affect neurotransmission via both pre- and post-synaptic mechanisms. Our data suggest that both PP1M and ROK influence synaptic transmission, but further studies are needed to give a full account of their mechanism of action. Journal of Neurochemistry

Original languageEnglish
Pages (from-to)84-99
Number of pages16
JournalJournal of neurochemistry
Volume123
Issue number1
DOIs
Publication statusPublished - okt. 1 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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