Identification of a novel tubulin-destabilizing protein related to the chaperone cofactor E.
Factors that regulate the microtubule cytoskeleton are critical in determining cell behavior. Here we describe the function of a novel protein that we term E-like based on its sequence similarity to the tubulin-specific chaperone cofactor E. We find that upon overexpression, E-like depolymerizes microtubules by committing tubulin to proteosomal degradation. Our data suggest that this function is direct and is based on the ability of E-like to disrupt the tubulin heterodimer in vitro. Suppression of E-like expression results in an increase in the number of stable microtubules and a tight clustering of endocellular membranes around the microtubule-organizing center, while the properties of dynamic microtubules are unaffected. These observations define E-like as a novel regulator of tubulin stability, and provide a link between tubulin turnover and vesicle transport.
Bartolini
Francesca
F
Department of Biochemistry, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA.
Tian
Guoling
G
Piehl
Michelle
M
Cassimeris
Lynne
L
Lewis
Sally A
SA
Cowan
Nicholas J
NJ
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D017173:Caenorhabditis elegans; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D020224:Expressed Sequence Tags; D020558:GTP Phosphohydrolases / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000502:physiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D034741:RNA, Small Interfering / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014162:Transfection; D014404:Tubulin / Q000737:chemistry
D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; C469270:TBCE protein, human; C503569:TBCEL protein, human; D014404:Tubulin; D049452:Green Fluorescent Proteins; D046988:Proteasome Endopeptidase Complex; D020558:GTP Phosphohydrolases