Molecular investigation of the MAST kinase family in the mammalian CNS

Abstract

Expression analysis of the whole MAST family has been performed using reverse-transcriptase PCR (RT-PCR), northern blot analysis and in situ hybridisation.   RT-PCR using cDNA derived from multiple mouse tissues has shown an overlapping expression pattern for MAST1 and 2, and a more distinct expression pattern for MAST3, 4 and MAST-like.  MAST1-4 were expressed in brain.  The expression of MAST1-4 in brain has been investigated using in situ hybridisation.  Again, MAST1 and 2 have been shown to have an overlapping pattern, which is in the cortex, hippocampus and cerebellum.  MAST 3 is expressed more strongly in the hippocampus, and it also shows a more distinct expression in the striatum.  MAST4 is expressed in both non-neuronal oligodendrocyte cells as well as hippocampal and cerebellar granule neurons.  The activity-dependent expression of MAST4 in the dentate gyrus has also been confirmed.  Although MAST1 and 2 have been shown to interact with group I and II metabotropic glutamate receptors via their PDZ domains this interaction does not appear to occur for MAST4.

MAST4 contains a noticeable extension of its C-terminus that is unique to this family member.  This ‘C-domain’ does not contain any identifiable domains and may contribute a novel function to this family member, which supports the known PDZ and kinase domain.

A model is proposed whereby MAST4 may contribute to transcription and/or alternative mRNA splicing following synaptic activity.  Based on these studies, possible new routes have been opened up to investigate the molecular mechanisms underlying neural signalling and plasticity.

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