Stomatin immunoreactivity in ciliated cells of the human airway epithelium.
Stomatin is a widely distributed 32kD membrane protein of unknown function. In biochemical studies it is associated with cholesterol+sphingomyelin-rich 'rafts' in the cytomembrane. Genetic studies in C. elegans, supported by microscopic studies in mammalian tissue and co-expression studies in oocytes, suggest a functional link with the DEG/ENaC (degenerin/epithelial Na+ channel) superfamily of monovalent ion channels. Since ENaC channels play a prominent role in the physiology of the respiratory epithelium, we have studied the immunolocalization of stomatin in mature and developing human airway epithelium by means of Western blot analysis, immunocytochemistry, and immunoelectron microscopy. Stomatin immunoreactivity (stomatin-IR) was found in the ciliated cells of the conductive airway epithelium in a distinct distribution pattern with the strongest signal along the cilia. Immunogold labelling revealed immunogold particles at the basal bodies, along the cilia, and at the membrane of the microvilli. The presence of stomatin-IR paralleled the stages of ciliogenesis in airway development, and its appearance preceded the elongation of the axoneme and the cilial outgrowth. Due to its presence in the different cellular locations in the ciliated cell, we suggest that stomatin is involved in various cellular functions. From its ultrastructural position, stomatin could be a candidate for a membrane-associated mechanotransducer with a role in the control of ciliary motility. Stomatin as a raft protein might be a microtubule associated protein moving along the outer surface of the microtubules to its terminal site of action in the cilia. Stomatin-IR in microvilli supports the hypothesis of a co-localization with beta- and gamma- ENaC and, in conclusion, their potential functional interaction to control the composition of periciliary mucus electrolytes.
Fricke
Britta
B
Department of Neuroanatomy, Institute of Anatomy MA 6/152, Ruhr University, Universitaetsstrasse 150, 44801 Bochum, Germany. britta.fricke@ruhr-uni-bochum.de
Stewart
Gordon W
GW
Treharne
Kathryn J
KJ
Mehta
Anil
A
Knöpfle
Gisela
G
Friedrichs
Nicolaus
N
Müller
Klaus-Michael
KM
von Düring
Monika
M
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D004573:Electrolytes / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D053503:Epithelial Sodium Channels; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism / Q000648:ultrastructure; D009093:Mucus / Q000378:metabolism; D020545:Respiratory Mucosa / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D015222:Sodium Channels / Q000378:metabolism
D001798:Blood Proteins; D004573:Electrolytes; D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C036860:STOM protein, human; D015222:Sodium Channels