Abstract
Kalirin is a multidomain guanine nucleotide exchange factor for small GTP binding proteins of the Rho family. It is expressed in multiple isoforms that contain different combinations of functional domains and display a complex pattern of expression during brain development. In addition to the isoforms generated through alternative splicing, we have identified multiple transcriptional start sites in rats and humans. These multiple transcriptional start sites result in full-length Kalirin transcripts possessing different 5′ ends encoding proteins with differing amino termini. These alternative first exons display different patterns of expression in developing rats and humans and in cultured cells. Most of these alternate first exons lie >100 kb upstream of exon 2 in both rats and humans. Comparisons of the rat and human Kalirin promoter regions reveal numerous shared potential regulatory elements.
Similar content being viewed by others
References
Alam, M. R., Johnson, R. C., Darlington, D. N., Hand, T. A., Mains, R. E., and Eippe, B. A. (1997) Kalirin, a cytosolic protein with Spectrin-like and GDP/GTP exchange factor-like domains that interacts with Peptidylglycine α-amidating Monooxygenase, an integral membrane peptide-processing enzyme. J. Biol. Chem. 272, 12667–12675.
Amalfitano, A., Rafael, J. A., and Chamberlain, J. S. (1997) Structure and mutation of the dystrophin gene, in Dystrophin: Gene, Protein, and Cell Biology, Cambridge University Press, Cambridge, U.K., pp. 1–26.
Aparicio, S., Chapman, J., Stupka, E., et al. (2002) Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science 297, 1301–1310.
Awasaki, T., Saito, M., Sone, M., et al. (2000) The Drosophila Trio plays an essential role in patterning of axons by regulating their directional extension. Neuron 26, 119–131.
Bailey, T. M. and Elkan, C. (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers, in Proceedings of the Second International Conference on Intelligent Systems for Molecular Biology, AAAI, Menlo Park, CA, pp. 28–36.
Bateman, J. and Van Vactor, D. (2001) The Trio family of guanine-nucleotide-exchange factors: regulators of axon guidance. J. Cell. Sci. 114, 1973–1980.
Bateman, J., Shu, H., and Van Vactor, D. (2000) The guanine nucleotide exchange factor Trio mediates axonal development in the Drosophila embryo. Neuron 26, 93–106.
Benachenhou, N., Massy, I., and Vacher, J. (2002) Characterization and expression analyses of the mouse Wiskott-Aldrich syndrome protein (WASP) family member Wave1/Scar. Gene 290, 131–140.
Colomer, V., Engeleander, S., Sharp, A. H., et al. (1997) Huntingtin-associated protein 1 (HAP1) binds to a Triolike polypeptide, with a rac1 guanine nucleotide exchange factor domain. Hum. Mol. Genet. 6, 1519–1525.
Debant, A., Serra-Pages, C., Seipel, K., et al. (1996) The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factors. Proc. Natl. Acad. Sci. USA 93, 5466–5471.
Gorecki, D. C., Monaco, A. P., Derry, J. M. J., Walker, A. P., Barnard, E. A., and Barnard, P. J. (1992) Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters. Hum. Mol. Genet. 1, 505–510.
Johnson, R. C., Penzes, P., Eipper, B. A., and Mains, R. E. (2000) Isoforms of Kalirin, a neuronal Db1 family member, generated through the use of different 5′- and 3′-ends along with an internal translational initiation site. J. Biol. Chem. 275, 19324–19333.
Lagutin, O. V., Zhu, C. C., Kobayashi, D., et al. (2003) Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Genes Dev. 17, 368–379.
Lau, F., Aldabe, R., Friedrich, V., Ohnishi, S., Yoshida, T., and Ramirez, F. (2001) Developmental expression of mouse Kruppel-like transcription factor KLF7 suggests a potential role in neurogenesis. Dev. Biol. 233, 305–318.
Lei, L., Ma, L., Nef, S., Thai, T., and Parada, L. F. (2001) MK1f7, a potential transcriptional regulator of TrkA nerve growth factor receptor expression in sensory and sympathetic neurons. Development 128, 1147–1158.
Liebl, E. C., Forsthoefel, D. J., Franco L. S., et al. (2000) Dosage-sensitive, reciprocal genetic interactions between the Abl tyrosine kinase and the putative GEF trio reveal trio’s role in axon pathfinding. Neuron 26, 107–118.
Luu, L., Ramshaw, H., Tahayato, A., Stuart, A., Jones, G., White, J., and Petkovich, M. (2001) Regulation of retinoic acid metabolism. Adv. Enzyme Regul. 41, 159–175.
Ma, X.-M., Johnson, R. C., Mains, R. E., and Eipper, B. A. (2001) Expression of Kalirin, a neuronal GDP/GTP exchange factor of the Trio family, in the central nervous system of the adult rat. J. Comp. Neurol. 429, 388–402.
Ma, X.-M., Mains, R. E., and Eipper, B. A. (2002) Plasticity in hippocampal peptidergic systems induced by repeated electroconvulsive shock. Neuropsychopharmacology 27, 55–71.
Maekawa, M., Ishikazi, T., Boku, S., et al. (1999) Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285, 895–898.
May, V., Schiller, M. R., Eipper, B. A., and Mains, R. E. (2002) Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms. J. Neurosci. 22, 6980–6990.
McPherson, C. E., Eipper, E. A., and Mains, R. E. (2002) Genomic organization and differential expression of Kalirin isoforms. Gene 284, 41–51.
Nomoto, S., Tatematsu, Y., Takahashi, T., and Osada, H. (1999) Cloning and characterization of the alternative promoter regions of the human LIMK2 gene responsible for alternative transcripts with tissue-specific expression. Gene 236, 259–271.
Pahlman, S., Hoehner, J. C., Nanberg, E., et al. (1995) Differentiation and survival influences of growth factors in human neuroblastoma. Eur. J. Cancer 31A, 453–458.
Pahlman, S., Mamaeva, S., Meyerson, G., et al. (1990) Human neuroblastoma cells in culture: a model for neuronal cell differentiation and function. Acta Physiol. Scand. Suppl. 592, 25–37.
Pozzoli, U., Elgar, G., Cagliani, R., et al. (2003) Comparative analysis of vertebrate dystrophin loci indicate intron gigantism as a common feature. Genome Res. 13, 764–772.
Seipel, K., Medle, Q. G., Kedersha, N. L., et al. (1999) Trio amino-terminal guanine nucleotide exchange factor domain expression promotes actin cytoskeleton reorganization, cell migration, and anchorage-dependent cell growth. J. Cell Sci. 112, 1825–1834.
Smale, S. T. (1994) Core promoter architecture for eukaryotic protein-coding genes, in Transcription: Mechanisms and Regulation, Conaway, R. C., and Conaway, J. W., eds., Raven, New York, pp. 63–81.
Steven, R., Kubiseski, T. J., Zheng, H., et al. (1998) UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans. Cell 92, 785–795.
Tatusova, T. A. and Madden, T. L. (1999) Blast 2 sequences—a new tool for comparing protein and nucleotide sequences. FEMS Microbiol. Lett. 174, 247–250.
Van Der Burg, B., Sonneveld, E., Lemmen, J. G., and Van Der Saag, P. T. (1999) Morphogenetic action of retinoids and estrogens. Int. J. Dev. Biol. 43, 735–743.
Zhu, C. C., Dyer, M. A., Uchikawa, M., Kondoh, H., Lagutin, O. V., and Oliver, G. (2002) Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors. Development 129, 2835–2849.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
McPherson, C.E., Eipper, B.A. & Mains, R.E. Kalirin expression is regulated by multiple promoters. J Mol Neurosci 22, 51–62 (2004). https://doi.org/10.1385/JMN:22:1-2:51
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/JMN:22:1-2:51