Abstract
Membrane palmitoylated proteins (MPPs) are a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). The ubiquitous expression and multidomain structure of MPPs provide the ability to form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing the proper cell structure, polarity and cell adhesion. The formation of MPP-dependent complexes in various cell types seems to be based on similar principles, but involves members of different protein groups, such as 4.1-ezrin-radixin-moesin (FERM) domain-containing proteins, polarity proteins or other MAGUKs, showing their multifaceted nature. In this review, we discuss the function of the MPP family in the formation of multiple protein complexes. Notably, we depict their significant role for cell physiology, as the loss of interactions between proteins involved in the complex has a variety of negative consequences. Moreover, based on recent studies concerning the mechanism of membrane raft formation, we shed new light on a possible role played by MPPs in lateral membrane organization.
Highlights
Membrane-associated guanylate kinases (MAGUKs) represent a diverse group of multidomain scaffolding proteins that are mainly present at sites of cell–cell contact and serve as platforms for numerous cellular processes including cell adhesion, cell signaling and cell polarity [1,2,3]
Further co-immunoprecipitation and pull-down experiments confirmed the binding of postsynaptic density (PSD)-95 with MPP2 through the Src homology 3 (SH3) and GUK domains of the latter [61]. These results suggested an interaction mechanism similar to that found for MPP1, as the D5 domain is located between SH3 and GUK domains [60]
Membrane palmitoylated proteins (MPPs) are scaffolding proteins from the membrane-associated guanylate kinases (MAGUKs) family, which can be found at the center of many biological processes—from the role in establishing cell structure, through maintaining cell junctions, cell polarity and regulation of cell signaling, to the probable main role in membrane raft formation mechanism
Summary
Membrane-associated guanylate kinases (MAGUKs) represent a diverse group of multidomain scaffolding proteins that are mainly present at sites of cell–cell contact and serve as platforms for numerous cellular processes including cell adhesion, cell signaling and cell polarity [1,2,3]. MPPs have only one PDZ domain with a length of approximately 80 amino acid residues (Figure 1a,b; depicted in dark blue) [16]. The binding site for ATP and GMP in MPPs (MPP1) is intact, which may suggest that nucleotides may have some regulatory role in GUK functions [12,27,28] These assumptions seem to be confirmed by reports about bacterially expressed GUK domain of MPP1, which showed little catalytic activity [1,11]. (d) the MPP5 PDZ/SH3/GUK tandem (for explanation of these abbreviations see the main text) bound to CRB–cytoplasmic tail (CT) (PDB ID: 4WSI) [25]; (e) the MPP5 L27N and Pals1-associated tight junction protein (PATJ) L27 heterodimer complex (PDB ID: 1VF6) [45]
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