Formation of Cell-Cell Channels

Project: Research project

Project Details

Description

ells in most tissues are interconnected by gap junction channels, which allow the passage of electrolytes
and small molecules from cell to cell. In some excitable cells these channels are involved in electrical
synaptic transmission and/or synchronization of electrical activity. In other tissues they are thought to pass
signal molecules and to couple the cells metabolically. In addition, as recent evidence suggests, some gap
unction proteins also form functional hemichannels, that under special circumstances, transiently connect
the cytoplasm with the extracellular space. Thus, gap junction proteins may mediate extracellular
communication in addition to their classical role of direct cell-to-cell communication.
The objective of this research project is to understand the permeation of small ions and molecules including
second messengers through gap junction channels and hemichannels formed by pannexin 1. Pannexin 1 is
a member of a recently discovered small family of proteins in vertebrates including humans capable of
forming hemichannels and gap junction channels in addition to the well characterized connexin family.
The first specific aim tests the hypothesis that the selective permeabilities of the channels formed by
connexins and pannexins are distinct and thus enable different functions of these proteins. The pore
dimensions of pannexin channels will be determined and compared to those of connexin channels. The
second aim tests the hypothesis that connexins and pannexins form channels of generally similar structure
with respect to membrane topology and location of pore forming moieties despite a lack of sequence
homology. The third aim is to identify moieties in the pannexin 1 sequence mediating calcium sensitivity.
Pannexin channels are activated by cytoplasmic calcium in the micromolar concentration range which
contrasts the inhibition or insensitivity of connexin channels to calcium.
Gap junction channels are known to be associated with a series of human diseases. Understanding their
molecular function is therefore relevant to the diagnosis and therapy of the diseases.
StatusFinished
Effective start/end date1/1/9411/30/11

Funding

  • National Institute of General Medical Sciences: $325,976.00
  • National Institute of General Medical Sciences: $323,013.00
  • National Institute of General Medical Sciences: $316,271.00
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences: $326,354.00

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