Duplicated zebrafish (Danio rerio) inositol phosphatases inpp5ka and inpp5kb diverged in expression pattern and function.
Duplicated zebrafish (Danio rerio) inositol phosphatases inpp5ka and inpp5kb diverged in expression pattern and function.
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DOI：
10.1007/s00427-023-00703-z
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发表时间：
2023-06
影响因子：
2.4
通讯作者：
Manzini, M. Chiara
中科院分区：
文献类型：
--
作者：
Shukla, Dhyanam;Gural, Brian M.;Cauley, Edmund S.;Battula, Namarata;Mowla, Shorbon;Karas, Brittany F.;Roberts, Llion E.;Cavallo, Luca;Turkalj, Luka;Moody, Sally A.;Swan, Laura E.;Manzini, M. Chiara
斑马鱼人类疾病模型开发的一个障碍是存在多个斑马鱼直系同源物，这些同源物是由硬骨鱼中的全基因组复制产生的。肌醇多磷酸5-磷酸酶K（INPP5K）突变导致以智力残疾、脑异常、白内障、肌肉疾病和身材矮小的可变表现为特征的综合征。INPP5K是一种磷酸酶，作用于磷酸肌醇的5位，以控制其稳态，并参与胰岛素信号传导、细胞骨架调节和蛋白质运输。以前，我们的团队和其他人已经通过靶向INPP 5K直系同源物inpp5ka和inpp5kb在斑马鱼敲除模型中复制了人类表型。在这里，我们表明，inpp5ka是更密切相关的直系同源人INPP5K。虽然inpp5ka和inpp5kb mRNA表达水平在发育中的头部、眼睛和尾部中遵循类似的趋势，但inpp5ka在这些组织中的表达比inpp5kb丰富得多。原位杂交显示了类似的趋势，也显示了独特的定位inpp5kb在松果体和视网膜不同的转录调控。我们还发现，inpp5kb已经失去了对它的首选底物，PtdIns（4，5）P2的催化活性。由于大多数人类突变是破坏磷酸酶活性的错义变化，我们建议单独的inpp5ka的丢失可以被靶向以概括人类的呈递。此外，我们发现inpp5kb的功能已经偏离inpp5ka，并可能在斑马鱼中发挥新的作用。在线版本包含补充材料，可通过10.1007/s00427 - 023 - 00703-z获得。
One hurdle in the development of zebrafish models of human disease is the presence of multiple zebrafish orthologs resulting from whole genome duplication in teleosts. Mutations in inositol polyphosphate 5-phosphatase K (INPP5K) lead to a syndrome characterized by variable presentation of intellectual disability, brain abnormalities, cataracts, muscle disease, and short stature. INPP5K is a phosphatase acting at position 5 of phosphoinositides to control their homeostasis and is involved in insulin signaling, cytoskeletal regulation, and protein trafficking. Previously, our group and others have replicated the human phenotypes in zebrafish knockdown models by targeting both INPP5K orthologs inpp5ka and inpp5kb. Here, we show that inpp5ka is the more closely related orthologue to human INPP5K. While both inpp5ka and inpp5kb mRNA expression levels follow a similar trend in the developing head, eyes, and tail, inpp5ka is much more abundantly expressed in these tissues than inpp5kb. In situ hybridization revealed a similar trend, also showing unique localization of inpp5kb in the pineal gland and retina indicating different transcriptional regulation. We also found that inpp5kb has lost its catalytic activity against its preferred substrate, PtdIns(4,5)P2. Since most human mutations are missense changes disrupting phosphatase activity, we propose that loss of inpp5ka alone can be targeted to recapitulate the human presentation. In addition, we show that the function of inpp5kb has diverged from inpp5ka and may play a novel role in the zebrafish. The online version contains supplementary material available at 10.1007/s00427-023-00703-z.
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影响因子：
11.4
作者：
Lukowski, Samuel W.;Lo, Camden Y.;Wong, Raymond C. B.
通讯作者：
Wong, Raymond C. B.
影响因子：
2
作者：
Piccinetti, Chiara Carla;Migliarini, Beatrice;Carnevali, Oliana
通讯作者：
Carnevali, Oliana
DOI：
10.1146/annurev-animal-030117-014821
发表时间：
2018-01-01
期刊：
ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 6
影响因子：
--
作者：
Ravi, Vydianathan;Venkatesh, Byrappa
通讯作者：
Venkatesh, Byrappa
影响因子：
14.5
作者：
Krieger, Michael;Roos, Andreas;Senderek, Jan
通讯作者：
Senderek, Jan
影响因子：
4.5
作者：
Livne, Zohar Ben-Moshe;Alon, Shahar;Gothilf, Yoav
通讯作者：
Gothilf, Yoav