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Newly synthesized polycystin-1 takes different trafficking pathways to the apical and ciliary membranes.
Gilder, Allison L; Chapin, Hannah C; Padovano, Valeria; Hueschen, Christina L; Rajendran, Vanathy; Caplan, Michael J.
Afiliação
  • Gilder AL; Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut.
  • Chapin HC; Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut.
  • Padovano V; Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut.
  • Hueschen CL; Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut.
  • Rajendran V; Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut.
  • Caplan MJ; Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut.
Traffic ; 19(12): 933-945, 2018 12.
Article em En | MEDLINE | ID: mdl-30125442
ABSTRACT
Mutations in the genes encoding polycystin-1 (PC1) and polycystin 2 (PC2) cause autosomal dominant polycystic kidney disease. These transmembrane proteins colocalize in the primary cilia of renal epithelial cells, where they may participate in sensory processes. PC1 is also found in the apical membrane when expressed in cultured epithelial cells. PC1 undergoes autocatalytic cleavage, producing an extracellular N-terminal fragment that remains noncovalently attached to the transmembrane C-terminus. Exposing cells to alkaline solutions elutes the N-terminal fragment while the C-terminal fragment is retained in the cell membrane. Utilizing this observation, we developed a "strip-recovery" synchronization protocol to study PC1 trafficking in polarized LLC-PK1 renal epithelial cells. Following alkaline strip, a new cohort of PC1 repopulates the cilia within 30 minutes, while apical delivery of PC1 was not detectable until 3 hours. Brefeldin A (BFA) blocked apical PC1 delivery, while ciliary delivery of PC1 was BFA insensitive. Incubating cells at 20°C to block trafficking out of the trans-Golgi network also inhibits apical but not ciliary delivery. These results suggest that newly synthesized PC1 takes distinct pathways to the ciliary and apical membranes. Ciliary PC1 appears to by-pass BFA sensitive Golgi compartments, while apical delivery of PC1 traverses these compartments.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Membrana Celular / Canais de Cátion TRPP Limite: Animals Idioma: En Revista: Traffic Assunto da revista: FISIOLOGIA Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Membrana Celular / Canais de Cátion TRPP Limite: Animals Idioma: En Revista: Traffic Assunto da revista: FISIOLOGIA Ano de publicação: 2018 Tipo de documento: Article