PT  - JOURNAL ARTICLE
AU  - Jean-Paul Borg
AU  - Manuel O. Lõpez-Figueroa
AU  - Mylène de Taddèo-Borg
AU  - Dallas E. Kroon
AU  - R. Scott Turner
AU  - Stanley J. Watson
AU  - Ben Margolis
TI  - Molecular Analysis of the X11–mLin-2/CASK Complex in Brain
AID  - 10.1523/JNEUROSCI.19-04-01307.1999
DP  - 1999 Feb 15
TA  - The Journal of Neuroscience
PG  - 1307--1316
VI  - 19
IP  - 4
4099  - http://www.jneurosci.org/content/19/4/1307.short
4100  - http://www.jneurosci.org/content/19/4/1307.full
SO  - J. Neurosci.1999 Feb 15; 19
AB  - A heterotrimeric complex containing Lin-10/X11α, Lin-2/CASK, and Lin-7 is evolutionarily conserved from worms to mammals. In Caenorhabditis elegans, it localizes Let-23, a receptor tyrosine kinase, to the basolateral side of vulval epithelium, a step crucial for proper vulva development. In mammals, the complex may also participate in receptor targeting in neurons. Accordingly, phosphotyrosine binding (PTB) and postsynaptic density-95/Discs large/Zona Occludens-1 domains found in X11α and mLin-2/CASK bind to cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. In this paper, we have further analyzed the X11α–mLin-2/CASK association that is mediated by a novel protein–protein interaction. We show that the mLin-2/CASK calmodulin kinase II (CKII) domain directly binds to a 63 amino acids peptide located between the Munc-18-1 binding site and the PTB domain in X11α. Ca2+/calmodulin association with mLin-2/CASK does not modify the X11α–mLin-2 interaction. A region containing the mLin-2/CASK guanylate kinase domain also interacts with X11α but with a lower affinity than the CKII domain. Immunostaining of X11α in the brain shows that the protein is expressed in areas shown previously to be positive for mLin-2/CASK staining. Together, our data demonstrate that the X11α–mLin-2 complex contacts many partners, creating a macrocomplex suitable for receptor targeting at the neuronal plasma membrane.