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Article
Identification of a Novel Lipopolysaccharide-Inducible Gene with Key Features of Both A Kinase Anchor Proteins and Chs1/beige Proteins
The Journal of Immunology
  • Jia-Wang Wang, University of South Florida
  • Julie Howson, University of South Florida
  • Edward M Haller, University of South Florida
  • William G Kerr, University of South Florida
Document Type
Article
Publication Date
4-1-2001
Digital Object Identifier (DOI)
https://doi.org/10.4049/jimmunol.166.7.4586
Abstract

Mutations in chs1/beige result in a deficiency in intracellular transport of vesicles that leads to a generalized immunodeficiency in mice and humans. The function of NK cells, CTL, and granulocytes is impaired by these mutations, indicating that polarized trafficking of vesicles is controlled by CHS1/beige proteins. However, a molecular explanation for this defect has not been identified. Here we describe a novel gene with orthologues in mice, humans, and flies that contains key features of both chs1/beige and A kinase anchor genes. We designate this novel gene lba for LPS-responsive, beige-like anchor gene. Expression of lba is induced after LPS stimulation of B cells and macrophages. In addition, lba is expressed in many other tissues in the body and has three distinct mRNA isoforms that are differentially expressed in various tissues. Strikingly, LBA-green-fluorescent protein (GFP) fusion proteins are localized to vesicles after LPS stimulation. Confocal microscopy indicates this protein is colocalized with the trans-Golgi complex and some lysosomes. Further analysis by immunoelectron microscopy demonstrates that LBA-GFP fusion protein can localize to endoplasmic reticulum, plasma membrane, and endocytosis vesicles in addition to the trans-Golgi complex and lysosomes. We hypothesize that LBA/CHS1/BG proteins function in polarized vesicle trafficking by guiding intracellular vesicles to activated receptor complexes and thus facilitate polarized secretion and/or membrane deposition of immune effector molecules.

Citation / Publisher Attribution

The Journal of Immunology, v. 166, issue 7, p. 4586-4595

Citation Information
Jia-Wang Wang, Julie Howson, Edward M Haller and William G Kerr. "Identification of a Novel Lipopolysaccharide-Inducible Gene with Key Features of Both A Kinase Anchor Proteins and Chs1/beige Proteins" The Journal of Immunology Vol. 166 Iss. 7 (2001) p. 4586 - 4595
Available at: http://works.bepress.com/edward_haller/22/