The postsynaptic spectrin/4.1 membrane protein "accumulation machine".
An important aspect of the function of the membrane-associated cytoskeleton has been suggested to be to trap and retain selected transmembrane proteins at points on the cell surface specified by cell adhesion molecules. In the process, cell adhesion molecules are cross-linked to each other, and so junctional complexes are strengthened. In this short review, we will discuss recent advances in understanding the role of this "accumulation machine" in postsynaptic structures. Function in the brain depends on correct ordering of synaptic intercellular junctions, and in particular the recruitment of receptors and other apparatus of the signalling system to postsynaptic membranes. Spectrin has long been known to be a component of postsynaptic densities, and recent advances in molecular cloning indicate that beta spectrins at PSDs are all "long" C-terminal isoforms characterised by pleckstrin homology domains. Isoforms of protein 4.1 are also present at synapses. All four 4.1 proteins are represented in PSD preparations, but it is 4.1R that is most enriched in PSDs. 4.1R binds to several proteins enriched in PSDs, including the characteristic PSD intermediate filament, alpha-internexin. Both 4.1 and spectrin interact with ionotropic glutamate receptors (AMPA and NMDA receptors, respectively): 4.1 stabilises AMPA receptors on the cell surface. By linking these receptors to the cytoskeletal and cell adhesion molecules that specify glutamatergic synapses, the membrane protein accumulation machine is suggested to direct the formation of postsynaptic signalling complexes.
Baines
A J
AJ
Department of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, UK.
Keating
L
L
Phillips
G W
GW
Scott
C
C
D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D009479:Neuropeptides; D011485:Protein Binding; D021381:Protein Transport; D017470:Receptors, Glutamate / Q000378:metabolism; D013049:Spectrin / Q000737:chemistry / Q000378:metabolism*; D013569:Synapses / Q000737:chemistry* / Q000378:metabolism*
D017487:Ankyrins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D017470:Receptors, Glutamate; C046643:alpha-internexin; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D013049:Spectrin