feh-1 and apl-1, the Caenorhabditis elegans orthologues of mammalian Fe65 and beta-amyloid precursor protein genes, are involved in the same pathway that controls nematode pharyngeal pumping.
feh-1 and apl-1, the Caenorhabditis elegans orthologues of mammalian Fe65 and beta-amyloid precursor protein genes, are involved in the same pathway that controls nematode pharyngeal pumping.
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feh-1 和 apl-1 是哺乳动物 Fe65 和 β-淀粉样前体蛋白基因的秀丽隐杆线虫直系同源物，参与控制线虫咽部泵送的同一途径。
DOI：
10.1242/jcs.115.7.1411
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发表时间：
2002
影响因子：
4
通讯作者：
P. Bazzicalupo
中科院分区：
文献类型：
--
作者：
N. Zambrano;M. Bimonte;S. Arbucci;D. Gianni;T. Russo;P. Bazzicalupo
哺乳动物Fe65s多基因家族编码三种具有相同模块化组织的高度相似蛋白：一个WW结构域和两个磷酸酪氨酸结合结构域。这些蛋白的PTB2结构域与阿尔茨海默病β -淀粉样蛋白前体蛋白APP和相关蛋白APLP1和APLP2的细胞质结构域结合，产生一个难以通过反向遗传学解剖的高度冗余系统。通过在秀丽隐杆线虫中寻找潜在的Fe65样基因，我们发现了一个单一基因feh-1 (Fe65同源基因-1)，该基因编码的蛋白质序列与哺乳动物的Fe65具有很高的相似性。FEH-1在功能上也与哺乳动物同源物相关；事实上，它的PTB2结构域与APL-1结合，APL-1是秀丽隐杆线虫APP同源物的产物。用特异性抗体染色表明，咽部的神经肌肉结构是FEH-1最高水平存在的部位。报道的表达研究表明，feh-1基因也在蛔虫神经元的一个子集中表达。我们产生并分离了feh-1的缺失等位基因，并且相应的纯合突变体在胚胎晚期或L1幼虫阶段被捕获，首次证明了fe65样基因在体内的重要作用。纯合子幼虫的咽部不收缩，幼虫不能进食。分析杂合子蠕虫和feh-1 rna干扰蠕虫的咽泵现象表明，feh-1功能的剂量影响线虫咽收缩率。干扰apl-1双链RNA对咽泵的影响相似，提示FEH-1和apl-1参与了相同的途径。线虫的非冗余系统将有助于研究Fe65-APP相互作用的基本生物学以及这一进化保守的相互作用蛋白系统所调节的分子事件。
The multigenic family of mammalian Fe65s encodes three highly similar proteins with the same modular organisation: a WW domain and two phosphotyrosine-binding domains. The PTB2 domain of these proteins binds to the cytosolic domains of the Alzheimer's beta-amyloid precursor protein APP and related proteins APLP1 and APLP2, generating a highly redundant system that is hard to dissect by reverse genetics. By searching potential Fe65-like genes in the nematode Caenorhabditis elegans, we identified a single gene, feh-1 (Fe65 homolog-1), encoding a protein with a high sequence similarity to mammalian Fe65s. FEH-1 is also functionally related to mammalian orthologues; in fact its PTB2 domain binds to APL-1, the product of the C. elegans orthologue of APP. Staining with specific antibodies show that the neuromuscular structures of the pharynx are the sites in which FEH-1 is present at highest levels. Expression studies with reporters indicate that the feh-1 gene is also expressed by a subset of the worm neurons. We generated and isolated a deletion allele of feh-1, and the corresponding homozygous mutants arrest as late embryos or as L1 larvae, demonstrating for the first time an essential role for a Fe65-like gene in vivo. The pharynx of homozygous larvae does not contract and the worms cannot feed. Analysis of pharyngeal pumping in heterozygous worms and in feh-1 RNA-interfered worms indicates that dosage of feh-1 function affects the rate of pharyngeal contraction in C. elegans. Interference with apl-1 double-stranded RNA showed a similar effect on pharyngeal pumping, suggesting that FEH-1 and APL-1 are involved in the same pathway. The non-redundant system of the nematode will prove useful for studying the basic biology of the Fe65-APP interaction and the molecular events regulated by this evolutionarily conserved system of interacting proteins.
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DOI：
10.1073/pnas.90.24.12045
发表时间：
1993-12-15
影响因子：
11.1
作者：
DAIGLE, I;LI, C
通讯作者：
LI, C
影响因子：
3.3
作者：
S. G. Clark;Xiaowei Lu;H. Horvitz
通讯作者：
S. G. Clark;Xiaowei Lu;H. Horvitz
影响因子：
56.9
作者：
Davis, MW;Fleischhauer, R;Avery, L
通讯作者：
Avery, L
秀丽隐杆线虫中兰尼碱受体通道的肌肉特异性功能。
影响因子：
4
作者：
Maryon,EB;Saari,B;Anderson,P
通讯作者：
Anderson,P
影响因子：
3.5
作者：
FIRE, A;HARRISON, SW;DIXON, D
通讯作者：
DIXON, D