Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain

Authors

  • Jesús Mariano Ureña,

    Corresponding author
    1. Developmental Neurobiology and Regeneration Lab, Institute of Biomedical Research of Barcelona–Parc Científic de Barcelona, and Department of Cell Biology, University of Barcelona, E08028 Barcelona, Spain
    • Developmental Neurobiology and Regeneration Lab, IRBB-Parc Científic de Barcelona, Josep Samitier 1-5, 08028 Barcelona, Spain
    Search for more papers by this author
  • Anna La Torre,

    1. Developmental Neurobiology and Regeneration Lab, Institute of Biomedical Research of Barcelona–Parc Científic de Barcelona, and Department of Cell Biology, University of Barcelona, E08028 Barcelona, Spain
    Search for more papers by this author
  • Albert Martínez,

    1. Developmental Neurobiology and Regeneration Lab, Institute of Biomedical Research of Barcelona–Parc Científic de Barcelona, and Department of Cell Biology, University of Barcelona, E08028 Barcelona, Spain
    Search for more papers by this author
  • Eve Lowenstein,

    1. Department of Dermatology, State University of New York Health Science Center at Brooklyn, New York 11203
    Search for more papers by this author
  • Neus Franco,

    1. Centre de Recerca Biomedica, Institut de Recerca en Ciencies de la Salut, Hospital Universitari de Sant Joan de Reus, E43201 Reus, Spain
    Search for more papers by this author
  • Raphaelle Winsky-Sommerer,

    1. Departments of Molecular Biology and Neuropharmacology, MB-10, The Scripps Research Institute, La Jolla, California 92037
    Search for more papers by this author
  • Xavier Fontana,

    1. Developmental Neurobiology and Regeneration Lab, Institute of Biomedical Research of Barcelona–Parc Científic de Barcelona, and Department of Cell Biology, University of Barcelona, E08028 Barcelona, Spain
    Search for more papers by this author
  • Ricardo Casaroli-Marano,

    1. Developmental Neurobiology and Regeneration Lab, Institute of Biomedical Research of Barcelona–Parc Científic de Barcelona, and Department of Cell Biology, University of Barcelona, E08028 Barcelona, Spain
    Search for more papers by this author
  • Miguel Angel Ibáñez-Sabio,

    1. Department of Biochemistry, Faculty of Medicine, University of Barcelona, E08071 Barcelona, Spain
    Search for more papers by this author
  • Marta Pascual,

    1. Developmental Neurobiology and Regeneration Lab, Institute of Biomedical Research of Barcelona–Parc Científic de Barcelona, and Department of Cell Biology, University of Barcelona, E08028 Barcelona, Spain
    Search for more papers by this author
  • José Antonio Del Rio,

    1. Developmental Neurobiology and Regeneration Lab, Institute of Biomedical Research of Barcelona–Parc Científic de Barcelona, and Department of Cell Biology, University of Barcelona, E08028 Barcelona, Spain
    Search for more papers by this author
  • Luis de Lecea,

    1. Departments of Molecular Biology and Neuropharmacology, MB-10, The Scripps Research Institute, La Jolla, California 92037
    Search for more papers by this author
  • Eduardo Soriano

    1. Developmental Neurobiology and Regeneration Lab, Institute of Biomedical Research of Barcelona–Parc Científic de Barcelona, and Department of Cell Biology, University of Barcelona, E08028 Barcelona, Spain
    Search for more papers by this author

Abstract

Cytosolic tyrosine kinases play a critical role both in neural development and in adult brain function and plasticity. Here we isolated a cDNA with high homology to human Ack1 and mouse Tnk2. This cDNA directs the expression of a 125-kD protein that can be autophosphorylated in tyrosines. Initially, this clone was named Pyk1 for proline-rich tyrosine kinase (Lev et al., 1995); however, since it corresponds to the mouse homolog of Ack1, here we called it Ack1/Pyk1. In this study we show that Ack1/Pyk1 mRNA and protein is highly expressed in the developing and adult brain. The highest levels of Ack1/Pyk1 expression were detected in the hippocampus, neocortex, and cerebellum. Electron microscopy studies showed that Ack1/Pyk1 protein is expressed in these regions both at dendritic spines and presynaptic axon terminals, indicating a role in synaptic function. Furthermore, we demonstrate that Ack1/Pyk1 mRNA levels are strongly upregulated by increased neural activity, produced by intraperitoneal kainate injections. During development, Ack1/Pyk1 was also expressed in the proliferative ventricular zones and in postmitotic maturing neurons. In neuronal cultures, Ack1/Pyk1 was detected in developing dendrites and axons, including dendritic tips and growth cones. Moreover, Ack1/Pyk1 colocalized with Cdc42 GTPase in neuronal cultures and coimmunoprecipitated with Cdc42 in HEK 293T cells. Altogether, our findings indicate that Ack1/Pyk1 tyrosine kinase may be involved both in adult synaptic function and plasticity and in brain development. J. Comp. Neurol. 490:119–132, 2005. © 2005 Wiley-Liss, Inc.

Ancillary