About this Research Topic
Multi-protein assemblies at the plasma membrane are functional protein machineries in numerous cellular processes. Malfunctioning of these protein assemblies is inextricably linked with diseases. In particular of vesicle trafficking, neurotransmission, immunoresponse, cell proliferation and cell death, a large diversity of protein assemblies have been identified, spanning from well-defined protein complexes (e.g. homo-/heterodimers and oligomers) to highly dynamical protein phase separations (e.g. signalosomes). Functionality of these protein assemblies at the plasma membrane relies on their structural and interactional features that are governed by biophysical principles. The most prominent molecular determinants can be specified as: (1) organization and orientation of protein complexes in respect to the membrane; (2) stoichiometry of the protein subunits; (3) kinetics of protein-protein interaction; (4) micro-compartmentalization with lipids, proteins and cortical actin meshwork at the plasma membrane; (5) partitioning of the cytosolic proteins; (6) interplays of 2-dimensional phase separation at the plasma membrane with the 3-dimensional liquid-liquid phase separation (LLPS) of cytosolic proteins.
Advances in single molecule methods have allowed investigating the membrane protein entities to gain tremendous mechanistic details on the regulatory mechanism. Single molecule fluorescence spectroscopy and microscopy have revealed the heterogeneity with accuracy down to individual molecules, thus contributing an unprecedented spatiotemporal resolution of protein reorganizations at the plasma membrane. Single molecule analyses in vitro and in live cells in terms of force spectroscopy, pH sensing, and surface potential sensing, as well as single molecule manipulations by optics or tips, have thrown new light on the structural and functional clues of protein assembling. Insights from these multi-dimensional biophysical aspects further extend the understanding of the molecular basis of membrane protein assembly.
In this Research Topic, we welcome both reviews and research articles to provide an overview of the current knowledge about the molecular mechanisms of protein assembly at the plasma membrane with broad functionalities. The scope of the Research Topic covers, but is not limited to, the following protein assemblies in the plasma membrane:
• Growth factors
• Morphogenetic proteins
• Pore-forming proteins
• Junctional proteins
• Synaptic neurotransmitter receptors
Additionally papers covering the development of single molecule experimental and analytical methodologies using state-of-art techniques that facilitate characterizing protein assembly in the plasma membrane are highly encouraged.
Keywords: Protein assembly, the plasma membrane, protein complex, phase separation, cytokine receptors, pore-forming proteins, morphogenetic proteins, immunity, cell death, stem cell regeneration
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