Stk36, also known as Fused, is a serine-threonine protein kinase. It is essential for the assembly and function of motile cilia and is associated with the Hedgehog (Hh) signaling pathway. Its proper function is crucial for processes like cerebrospinal fluid (CSF) flow, ciliogenesis, and ovum transport, and its dysregulation can lead to diseases such as primary ciliary dyskinesia (PCD) [1,3,4,5,6].

In gene knockout (KO) studies, both Stk36tmE4-/-mice and Ulk4tm1a/tm1a mice developed progressive hydrocephalus postnatally and had dysfunctional CSF flow, with multiple motile cilia defects [4]. In the flagellated protist Leishmania mexicana, both LmxULK4 and LmxFused (Stk36) KO mutants exhibited flagellum cytoskeleton structural defects [1]. In an Australian Shepherd dog with PCD, a homozygous single base-pair exchange at a splice site of STK36 was found, leading to aberrant splicing [2].

In conclusion, Stk36 is vital for ciliogenesis, cilia function, and CSF flow as shown by model-based research. Its KO mouse models contribute to understanding diseases like hydrocephalus and PCD, highlighting its significance in these disease areas.

References:

1. McCoy, Ciaran J, Paupelin-Vaucelle, Humbeline, Gorilak, Peter, Varga, Vladimir, Gluenz, Eva. 2023. ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum. In Molecular biology of the cell, 34, ar66. doi:10.1091/mbc.E22-06-0222. https://pubmed.ncbi.nlm.nih.gov/36989043/

2. Christen, Matthias, Ludwig-Peisker, Odette, Jagannathan, Vidhya, Schönball, Ulrike, Leeb, Tosso. 2023. STK36 splice site variant in an Australian Shepherd dog with primary ciliary dyskinesia. In Animal genetics, 54, 412-415. doi:10.1111/age.13306. https://pubmed.ncbi.nlm.nih.gov/36786090/

3. Zhou, Mengmeng, Han, Yuhong, Jiang, Jin. 2023. Ulk4 promotes Shh signaling by regulating Stk36 ciliary localization and Gli2 phosphorylation. In eLife, 12, . doi:10.7554/eLife.88637. https://pubmed.ncbi.nlm.nih.gov/38096226/

4. Zhang, Hongye, Yang, Meimei, Zhang, Jianhua, Liu, Min, Han, Yongfeng. . The putative protein kinase Stk36 is essential for ciliogenesis and CSF flow by associating with Ulk4. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, e23138. doi:10.1096/fj.202300481R. https://pubmed.ncbi.nlm.nih.gov/37584603/

5. Nozawa, Yoko Inès, Yao, Erica, Lin, Chuwen, Gacayan, Rhodora, Chuang, Pao-Tien. 2013. Fused (Stk36) is a ciliary protein required for central pair assembly and motile cilia orientation in the mammalian oviduct. In Developmental dynamics : an official publication of the American Association of Anatomists, 242, 1307-19. doi:10.1002/dvdy.24024. https://pubmed.ncbi.nlm.nih.gov/23907739/

6. Edelbusch, Christine, Cindrić, Sandra, Dougherty, Gerard W, Amirav, Israel, Omran, Heymut. 2017. Mutation of serine/threonine protein kinase 36 (STK36) causes primary ciliary dyskinesia with a central pair defect. In Human mutation, 38, 964-969. doi:10.1002/humu.23261. https://pubmed.ncbi.nlm.nih.gov/28543983/