Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation.
Hypoparathyroidism, mental retardation and facial dysmorphism (HRD) is a fatal developmental disease caused by mutations in tubulin-specific chaperone E (TBCE). A mouse Tbce mutation causes progressive motor neuronopathy. To dissect the functions of TBCE and the pathogenesis of HRD, we generated mutations in Drosophila tbce, and manipulated its expression in a tissue-specific manner. Drosophila tbce nulls are embryonic lethal. Tissue-specific knockdown and overexpression of tbce in neuromusculature resulted in disrupted and increased microtubules, respectively. Alterations in TBCE expression also affected neuromuscular synapses. Genetic analyses revealed an antagonistic interaction between TBCE and the microtubule-severing protein Spastin. Moreover, treatment of muscles with the microtubule-depolymerizing drug nocodazole implicated TBCE as a tubulin polymerizing protein. Taken together, our results demonstrate that TBCE is required for the normal development and function of neuromuscular synapses and that it promotes microtubule formation. As defective microtubules are implicated in many neurological and developmental diseases, our work on TBCE may offer novel insights into their basis.
Jin
Shan
S
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Pan
Luyuan
L
Liu
Zhihua
Z
Wang
Qifu
Q
Xu
Zhiheng
Z
Zhang
Yong Q
YQ
D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008124:Locomotion; D008870:Microtubules / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000378:metabolism*
D029721:Drosophila Proteins; D018832:Molecular Chaperones; C541489:tubulin-specific chaperone E, Drosophila