Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins

Yu Li, Jingliang Yan, Pradip De, Hua Chen Chang, Akira Yamauchi, Kent W. Christopherson, Nivanka C. Paranavitana, Xiaodong Peng, Chaekyun Kim, Veerendra Munugulavadla, Reuben Kapur, Hanying Chen, Weinian Shou, James C. Stone, Mark H. Kaplan, Mary C. Dinauer, Donald L Durden, Lawrence A. Quilliam

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Abstract

The Ras-related GTPases Rap1a and 1b have been implicated in multiple biological events including cell adhesion, free radical production, and cancer. To gain a better understanding of Rap1 function in mammalian physiology, we deleted the Rap1a gene. Although loss of Rap1a expression did not initially affect mouse size or viability, upon backcross into C57BL/6J mice some Rap1a -/- embryos died in utero. T cell, B cell, or myeloid cell development was not disrupted in Rap1a -/- mice. However, macrophages from Rap1a null mice exhibited increased haptotaxis on fibronectin and vitronectin matrices that correlated with decreased adhesion. Chemotaxis of lymphoid and myeloid cells in response to CXCL12 or CCL21 was significantly reduced. In contrast, an increase in FcR-mediated phagocytosis was observed. Because Rap1a was previously copurified with the human neutrophil NADPH oxidase, we addressed whether GTPase loss affected superoxide production. Neutrophils from Rap1a -/- mice had reduced fMLP-stimulated superoxide production as well as a weaker initial response to phorbol ester. These results suggest that, despite 95% amino acid sequence identity, similar intracellular distribution, and broad tissue distribution, Rap1a and 1b are not functionally redundant but rather differentially regulate certain cellular events.

Original languageEnglish (US)
Pages (from-to)8322-8331
Number of pages10
JournalJournal of Immunology
Volume179
Issue number12
DOIs
StatePublished - Dec 15 2007

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rap1 GTP-Binding Proteins
Myeloid Cells
Chemotaxis
Superoxides
Neutrophils
Vitronectin
Monomeric GTP-Binding Proteins
NADPH Oxidase
GTP Phosphohydrolases
Phorbol Esters
Tissue Distribution
Inbred C57BL Mouse
Fibronectins
Phagocytosis
Cell Adhesion
Free Radicals
Amino Acid Sequence
B-Lymphocytes
Embryonic Structures
Macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Li, Y., Yan, J., De, P., Chang, H. C., Yamauchi, A., Christopherson, K. W., ... Quilliam, L. A. (2007). Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins. Journal of Immunology, 179(12), 8322-8331. https://doi.org/10.4049/jimmunol.179.12.8322

Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins. / Li, Yu; Yan, Jingliang; De, Pradip; Chang, Hua Chen; Yamauchi, Akira; Christopherson, Kent W.; Paranavitana, Nivanka C.; Peng, Xiaodong; Kim, Chaekyun; Munugulavadla, Veerendra; Kapur, Reuben; Chen, Hanying; Shou, Weinian; Stone, James C.; Kaplan, Mark H.; Dinauer, Mary C.; Durden, Donald L; Quilliam, Lawrence A.

In: Journal of Immunology, Vol. 179, No. 12, 15.12.2007, p. 8322-8331.

Research output: Contribution to journalArticle

Li, Y, Yan, J, De, P, Chang, HC, Yamauchi, A, Christopherson, KW, Paranavitana, NC, Peng, X, Kim, C, Munugulavadla, V, Kapur, R, Chen, H, Shou, W, Stone, JC, Kaplan, MH, Dinauer, MC, Durden, DL & Quilliam, LA 2007, 'Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins', Journal of Immunology, vol. 179, no. 12, pp. 8322-8331. https://doi.org/10.4049/jimmunol.179.12.8322
Li, Yu ; Yan, Jingliang ; De, Pradip ; Chang, Hua Chen ; Yamauchi, Akira ; Christopherson, Kent W. ; Paranavitana, Nivanka C. ; Peng, Xiaodong ; Kim, Chaekyun ; Munugulavadla, Veerendra ; Kapur, Reuben ; Chen, Hanying ; Shou, Weinian ; Stone, James C. ; Kaplan, Mark H. ; Dinauer, Mary C. ; Durden, Donald L ; Quilliam, Lawrence A. / Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins. In: Journal of Immunology. 2007 ; Vol. 179, No. 12. pp. 8322-8331.
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