The Carboxyl Tail of Connexin32 Regulates Gap Junction Assembly in Human Prostate and Pancreatic Cancer Cells
| Autor: | Anuttoma Ray, Parmender P. Mehta, Brett J. Roberts, Shalini Mitra, Linda S. Kelsey, Parul Katoch, James K. Wahl, Keith R. Johnson |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cellular differentiation Connexin Biology Biochemistry Cell junction Gap junction assembly Connexins Permeability Cell Line Tumor otorhinolaryngologic diseases Humans Cell adhesion Molecular Biology urogenital system Gap junction Gap Junctions Prostatic Neoplasms Cell Biology Transmembrane protein Neoplasm Proteins Protein Structure Tertiary Cell biology Gene Expression Regulation Neoplastic Pancreatic Neoplasms Cytoplasm sense organs |
| Zdroj: | Journal of Biological Chemistry. 290:4647-4662 |
| ISSN: | 0021-9258 |
| Popis: | Connexins, the constituent proteins of gap junctions, are transmembrane proteins. A connexin (Cx) traverses the membrane four times and has one intracellular and two extracellular loops with the amino and carboxyl termini facing the cytoplasm. The transmembrane and the extracellular loop domains are highly conserved among different Cxs, whereas the carboxyl termini, often called the cytoplasmic tails, are highly divergent. We have explored the role of the cytoplasmic tail of Cx32, a Cx expressed in polarized and differentiated cells, in regulating gap junction assembly. Our results demonstrate that compared with the full-length Cx32, the cytoplasmic tail-deleted Cx32 is assembled into small gap junctions in human pancreatic and prostatic cancer cells. Our results further document that the expression of the full-length Cx32 in cells, which express the tail-deleted Cx32, increases the size of gap junctions, whereas the expression of the tail-deleted Cx32 in cells, which express the full-length Cx32, has the opposite effect. Moreover, we show that the tail is required for the clustering of cell-cell channels and that in cells expressing the tail-deleted Cx32, the expression of cell surface-targeted cytoplasmic tail alone is sufficient to enhance the size of gap junctions. Our live-cell imaging data further demonstrate that gap junctions formed of the tail-deleted Cx32 are highly mobile compared with those formed of full-length Cx32. Our results suggest that the cytoplasmic tail of Cx32 is not required to initiate the assembly of gap junctions but for their subsequent growth and stability. Our findings suggest that the cytoplasmic tail of Cx32 may be involved in regulating the permeability of gap junctions by regulating their size. |
| Databáze: | OpenAIRE |
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