PSD95beta regulates plasma membrane Ca2+ pump localization at the photoreceptor synapse.
At the presynaptic plasma membrane of the photoreceptor the correct localization of the calcium extruder, plasma membrane Ca2+-ATPase (PMCA), is determined by a unique protein complex. Here, the role of two proteins within the complex; membrane palmitoylated protein 4 (MPP4) and postsynaptic density protein 95 (PSD95) is investigated in more details, using Mpp4 and Psd95 mutant mice. MPP4 deficiency results in the loss of both PMCA and PSD95 from the photoreceptor synapse. Truncation of the C-terminal part of MPP4 leads to a loss of PSD95 and mislocalization of PMCA, while truncation of the C-terminal part of PSD95 did not affect the localization of the complex members. Lentivirus-mediated molecular replacement strategy was used to selectively express either PSD95alpha or PSD95beta in wild type or Mpp4 mutant primary retinal explants. Silencing of the Psd95 gene resulted in the loss of presynaptic MPP4 and PMCA1. The plasma membrane localization of MPP4 and PMCA1 could be restored by the expression of PSD95beta. We conclude that both scaffold proteins PSD95beta and MPP4 are essential for the modulation of PMCA levels at the presynaptic plasma membrane and thereby influence the photoreceptor synaptic calcium handling.
Aartsen
Wendy M
WM
Department of Neuromedical Genetics, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
Arsanto
Jean-Pierre
JP
Chauvin
Jean-Paul
JP
Vos
Rogier M
RM
Versteeg
Inge
I
Cardozo
Bob Nunes
BN
Bivic
André Le
AL
Wijnholds
Jan
J
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010786:Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; C477071:Mpp4 protein, mouse; D011993:Recombinant Fusion Proteins; D051528:Guanylate Kinases; D053499:Plasma Membrane Calcium-Transporting ATPases