RT Journal Article
SR Electronic
T1 Regulated Cationic Channel Function in <em>Xenopus</em>Oocytes Expressing <em>Drosophila</em> Big Brain
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2530
OP 2540
DO 10.1523/JNEUROSCI.22-07-02530.2002
VO 22
IS 7
A1 Gina M. Yanochko
A1 Andrea J. Yool
YR 2002
UL http://www.jneurosci.org/content/22/7/2530.abstract
AB Big brain (bib) is a neurogenic gene that when mutated causes defects in cell fate determination duringDrosophila 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 inXenopus oocytes provides a voltage-insensitive, nonselective cation channel function with permeability to K+ &gt; 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.