Ever hear of membrane-associated guanylate kinases? I’ll let one team of researchers describe them:
Membrane-associated guanylate kinases (MAGUKs) form a family of scaffolding proteins, engaged in the organisation of multiprotein complexes, which are often associated with cellular junctions or signalling complexes, such as the vertebrate tight junction (TJ) or the Drosophila septate junction (SJ) in epithelial cells or the neuromuscular junction (NMJ). Their capacity to serve as a platform for recruiting larger protein assemblies results from the presence of several protein-protein interaction domains: one to three PDZ (PSD-95/Discs large/zonula occludens (ZO)-1)-domains, an SH3-(Src homology-3)-domain and a guanylate kinase (GUK)-domain. Some members additionally contain one or two L27 (Lin-2/Lin-7)-domains in their N-terminus.. This modular structure is ideally suited to recruit a variety of components into a protein complex, the composition of which often depends on the cell type and/or developmental stage. In addition, MAGUK-encoding genes often give rise to more than one isoform by alternative splicing, thus increasing the possibility of multiple interactions, localisations and/or functions. [1]
So we have a modular scaffold protein that associates with protein complexes involved in connecting cells together. It is “ideally suited to recruit a variety of components into a protein complex” and its structure is poised to be exploited by alternative splicing. The MAGUKs play important regulatory roles in this multicellular context, “where they coordinate multiple binding partners, including cell adhesion molecules and ion channels.” [2] The MAGUKs thus link these interactions to downstream signaling events. Not surprisingly, they play an important role in brain function:
In the postsynaptic density of excitatory glutamatergic synapses, membrane associated guanylate kinase (MAGUK) proteins, such as Post-Synaptic Density 95 (PSD-95), organize ionotropic glutamate receptors and their associated signalling proteins regulating the strength of synaptic activity. Modifications of MAGUK proteins function in the glutamatergic synapse such as alterations of MAGUK proteins interaction with N-Methyl-D-Aspartate (NMDA) receptors regulatory subunits are common events in several neurodegenerative disorders. Thus, a better knowledge and understanding of MAGUK structure and function as well as of the molecular events regulating MAGUK-mediated interactions in the glutamatergic synapse could lead to the identification of new targets for pharmaceutical intervention for neurodegenerative diseases. [3]
It would seem that the MAGUKs would be a very useful component of any genomic toolkit that was front-loaded to facilitate the emergence of metazoan life. So when did these MAGUKs originate?
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