The Journal of Neuroscience, April 1, 2002, 22(7):2530-2540
Regulated Cationic Channel Function in Xenopus
Oocytes Expressing Drosophila Big Brain
Gina M.
Yanochko1 and
Andrea J.
Yool1, 2
1 Program in Pharmacology and Toxicology and
2 Departments of Pharmacology and Physiology, College of
Medicine, University of Arizona, Tucson, Arizona 85724-5051
Big brain (bib) is a neurogenic gene
that when mutated causes defects in cell fate determination during
Drosophila neurogenesis through an unknown mechanism.
The protein Big Brain (BIB) has sequence identity with the major
intrinsic protein family that includes the water- and ion-conducting
aquaporin channels. We show here that BIB expressed heterologously in
Xenopus oocytes provides a voltage-insensitive,
nonselective cation channel function with permeability to
K+ > Na+ 
tetraethylammonium. The conductance, activated in response to
endogenous signaling pathways in BIB-expressing oocytes, is decreased
after treatment with 20 µM insulin and is enhanced with 10 µM lavendustin A, a tyrosine kinase inhibitor. Western
blot analysis confirms that BIB is tyrosine-phosphorylated. Both
tyrosine phosphorylation and the potentiating effect of lavendustin A
are removed by partial deletion of the C terminus (amino acids
317-700). Current activation is not observed in control oocytes or in
oocytes expressing a nonfunctional mutant (BIB E71N) that appears to be expressed on the plasma membrane by confocal microscopy and Western blotting. These results indicate that BIB can participate in tyrosine kinase-regulated transmembrane signaling and may suggest a role for
membrane depolarization in the neurogenic function of BIB in early development.
Key words:
major intrinsic protein; Xenopus oocyte; tyrosine kinase; voltage clamp; neurogenic; aquaporin
Copyright © 2002 Society for Neuroscience 0270-6474/02/2272530-11$05.00/0
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