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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900792v1 183/3/1675    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Gorska, M. M. Articles by Alam, R. PubMed PubMed Citation Articles by Gorska, M. M. Articles by Alam, R.

Uncoordinated 119 Protein Controls Trafficking of Lck via the Rab11 Endosome and Is Critical for Immunological Synapse Formation¹

Magdalena M. Gorska^*,, Qiaoling Liang^*, Zunayet Karim^* and Rafeul Alam^2,*,

^* Division of Allergy and Immunology, Department of Medicine, National Jewish Health (formerly National Jewish Medical and Research Center), Denver, CO 80206; and Division of Allergy and Immunology, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO 80206

The activation of T cells through the TCR is essential for development of the adaptive immune response. TCR does not have any enzymatic activity and relies on the plasma membrane-associated lymphocyte-specific protein tyrosine kinase (Lck) for initiation of signaling. Here we uncover a mechanism that is responsible for plasma membrane targeting of Lck. We show that Lck is transported to the membrane via a specific endosomal compartment. The transport depends on the adaptor protein Uncoordinated 119 (Unc119), on the GTPase rat brain 11 (Rab11), and on the actin cytoskeleton. Unc119 regulates the activation of Rab11. Consequently, Unc119 orchestrates the recruitment of the actin-based motor protein, myosin 5B, and the organization of multiprotein complexes on endosomes. The Unc119-regulated pathway is essential for immunological synapse formation and T cell activation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants RO1 AI0059719 and RO1 AI68088 (to R.A. and M.M.G.) and PPG HL36577 and N01 HHSN272200700048C (to R.A.).

² Address correspondence and reprint requests to Dr. Rafeul Alam, Division of Allergy and Immunology, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206. E-mail address: alamr{at}njhealth.org

³ Abbreviations used in this paper: Src, Rous sarcoma oncogene homolog; IS, immunological synapse; Lck, lymphocyte-specific protein tyrosine kinase; Rab11, ras gene from rat brain 11; Unc119, Uncoordinated 119; HA, hemagglutinin; siRNA, small interfering RNA; shRNA, small haipin RNA; CTB, subunit B of cholera toxin; SED, staphylococcal enterotoxin D.

⁴ The online version of this article contains supplemental material.