Podocalyxin is a novel polysialylated neural adhesion protein with multiple roles in neural development and synapse formation.
Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-of-function reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development.
Vitureira
Nathalia
N
Institute for Research in Biomedicine, Parc Cientific de Barcelona, Barcelona, Spain.
Andrés
Rosa
R
Pérez-Martínez
Esther
E
Martínez
Albert
A
Bribián
Ana
A
Blasi
Juan
J
Chelliah
Shierley
S
López-Doménech
Guillermo
G
De Castro
Fernando
F
Burgaya
Ferran
F
McNagny
Kelly
K
Soriano
Eduardo
E
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011247:Pregnancy; D012794:Sialic Acids / Q000378:metabolism; D012795:Sialoglycoproteins / Q000172:deficiency / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D020558:GTP Phosphohydrolases; D019006:Neural Cell Adhesion Molecules; D010750:Phosphoproteins; D012794:Sialic Acids; D012795:Sialoglycoproteins; D017923:Sodium-Hydrogen Exchangers; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000099149:Ezrin; C489577:Rhog protein, mouse; C001643:podocalyxin; C093376:sodium-hydrogen exchanger regulatory factor