Intragenic suppressors of unc-104 ( e1265 ) identify potential roles of the conserved stalk region.
Intragenic suppressors of unc-104 ( e1265 ) identify potential roles of the conserved stalk region.
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DOI：
10.17912/micropub.biology.000539
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发表时间：
2022
影响因子：
--
通讯作者：
Jin, Yishi
中科院分区：
文献类型：
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作者：
Byrd, Dana T;Pearlman, Julie M;Jin, Yishi
KIF-104及其哺乳动物直系同源物KIF 1A是微管马达蛋白，其需要将突触囊泡前体从神经元细胞体移动到突触前位点。这些马达蛋白由N-末端马达结构域、随后的颈部区域、三个卷曲螺旋结构域和FHA结构域以及C-末端PH结构域组成。卷曲螺旋3和PH结构域之间是一个大的未表征区域，称为茎。In C. elegans UNC-104（E1265）是一种部分丧失功能的突变体，突触囊泡保留在细胞体中，并且在突触前位点不存在。unc-104（e1265）在PH结构域中含有氨基酸取代D1497 N，并且突变蛋白显示降低的PI（4，5）P（2）结合。通过遗传抑制基因筛选，我们确定了在茎的保守区域，导致unc-104（e1265）的基因内抑制氨基酸取代。目前，对茎区的功能知之甚少。我们的研究结果意味着潜在的补偿或拮抗之间的相互作用的柄区和货物结合PH结构域。
UNC-104 and its mammalian ortholog, KIF1A, are microtubule motor proteins required for moving synaptic vesicle precursors from neuronal cell bodies to presynaptic sites. These motor proteins consist of N-terminal motor domain, followed by a neck region, three coiled-coil domains and a FHA domain, and a C-terminal PH domain. Between the coiled-coil 3 and the PH domain is a large uncharacterized region called stalk. In C. elegans unc-104 ( e1265 ), a partial loss of function mutant, synaptic vesicles are retained in the cell body and absent from presynaptic sites. unc-104 ( e1265 ) contains amino acid substitution D1497N in the PH domain and the mutant proteins show reduced PI(4,5)P(2) binding. Through genetic suppressor screening, we identified amino acid substitutions in a conserved region of the stalk that cause intragenic suppression of unc-104 ( e1265 ). Currently, little is known about the functions of the stalk region. Our findings imply potential compensatory or antagonistic interaction between the stalk region and the cargo binding PH domain.