title: Protein 4.1N does not interact with the inositol 1,4,5-trisphosphate receptor in an epithelial cell line.
abstract: Cytosolic Ca2+ regulates a variety of cell functions, and the spatial patterns of Ca2+ signals are responsible in part for the versatility of this second messenger. The subcellular distribution of the inositol 1,4,5-trisphosphate receptor (IP3R) is thought to regulate Ca2+-signaling patterns but little is known about how the distribution of the IP3R itself is regulated. Here we examined the relationship between the IP3R and the cytoskeletal linker protein 4.1N in the polarized WIF-B cell line because protein 4.1N regulates targeting of the type I IP3R in neurons, but WIF-B cells do not express this cytoskeletal protein. WIF-B cells expressed all three isoforms of the IP3R, and each isoform was distributed throughout the cell. These cells did not express the ryanodine receptor. Photorelease of microinjected, caged IP3 induced a rapid rise in cytosolic Ca2+, but the increase began uniformly throughout the cell rather than at a specific initiation site. Expression of protein 4.1N was not associated with redistribution of the IP3R or changes in Ca2+-signaling patterns. These findings are consistent with the hypothesis that the subcellular distribution of IP3R isoforms regulates the formation of Ca2+ waves, and the finding that interactions between protein 4.1N and the IP3R vary among cell types may provide an additional, tissue-specific mechanism to shape the pattern of Ca2+ waves.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Sona
authors.initials: S
authors.lastname: Sehgal
authors.forename: Mateus T
authors.initials: MT
authors.lastname: Guerra
authors.forename: Emma A
authors.initials: EA
authors.lastname: Kruglov
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Michael H
authors.initials: MH
authors.lastname: Nathanson
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; C488910:Itpr1 protein, rat; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009479:Neuropeptides; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; C120557:erythrocyte membrane protein band 4.1-like 1