Rab38 targets to lamellar bodies and normalizes their sizes in lung alveolar type II epithelial cells. 2011

Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104-6068, USA.

Rab38 is a rat Hermansky-Pudlak syndrome gene that plays an important role in surfactant homeostasis in alveolar type II (ATII) pneumocytes. We examined Rab38 function in regulating lamellar body (LB) morphology in ATII cells. Quantitative electron microscopy revealed that LBs in ATII cells were ∼77% larger in Rab38-null fawn-hooded hypertension (FHH) than control Sprague-Dawley (SD) rats. Rab38 protein expression was restricted in lung epithelial cells but was not found in primary endothelial cells. In SD ATII cells, Rab38 protein level gradually declined during 5 days in culture. Importantly, endogenous Rab38 was present in LB fractions purified from SD rat lungs, and transiently expressed enhanced green fluorescent protein (EGFP)-tagged Rab38 labeled only the limiting membranes of a subpopulation (∼30%) of LBs in cultured ATII cells. This selective targeting was abolished by point mutations to EGFP-Rab38 and was not shared by Rab7 and Rab4b, which also function in the ATII cells. Using confocal microscopy, we established a method for quantitative evaluation of the enlarged LB phenotype temporally preserved in cultured FHH ATII cells. A direct causal relationship was established when the enlarged LB phenotype was reserved and then rescued by transiently reexpressed EGFP-Rab38 in cultured FHH ATII cells. This rescuing effect was associated with dynamic EGFP-Rab38 targeting to and on LB limiting membranes. We conclude that Rab38 plays an indispensible role in maintaining LB morphology and surfactant homeostasis in ATII pneumocytes.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D011650 Pulmonary Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Alveoli, Pulmonary,Alveolus, Pulmonary,Pulmonary Alveolus
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D000090802 rab7 GTP-Binding Proteins A small family of rab GTP-binding proteins that play a key role in membrane trafficking in the late endocytic and autophagic pathways. Rab7 Proteins,ras-Related Protein Rab-7,GTP-Binding Proteins, rab7,Protein Rab-7, ras-Related,Proteins, Rab7,Proteins, rab7 GTP-Binding,Rab-7, ras-Related Protein,rab7 GTP Binding Proteins,ras Related Protein Rab 7
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
April 1996, The American journal of physiology,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
January 1979, Pathologica,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
May 2012, American journal of physiology. Lung cellular and molecular physiology,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
January 1975, Tissue & cell,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
September 2001, Journal of biochemistry,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
March 1980, Thorax,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
April 1988, European journal of cell biology,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
March 2004, American journal of respiratory cell and molecular biology,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
April 1988, Experimental and molecular pathology,
Linghui Zhang, and Kevin Yu, and Kyle W Robert, and Kristine M DeBolt, and Nankang Hong, and Jian-Qin Tao, and Mitsunori Fukuda, and Aron B Fisher, and Shaohui Huang
February 2024, Toxicology in vitro : an international journal published in association with BIBRA,
Copied contents to your clipboard!