Klc3, a kinesin light chain, is involved in cargo transport along microtubules. It has specific functions in spermatogenesis and ciliary trafficking, and may be associated with Alzheimer's disease and some cancers. Its role in spermatogenesis is related to sperm tail midpiece formation, while in ciliary trafficking, it interacts with CILK1, a ciliary gene [2,3,4,5].

In a Cilk1 -deficient mouse model, Klc3 was identified as a regulator of ciliary trafficking and cyst progression. Klc3 interacts with CILK1 at cilia bases, and its overexpression promotes ciliary recruitment of IFT-B and EGFR in CILK1 deficiency, contributing to ciliary defects in cystogenesis. Reducing Klc3 rescued ciliary defects and inhibited cyst progression caused by CILK1 deficiency [1]. In transgenic mouse models for spermatid-specific Klc3ΔHR mutant protein expression, male transgenic mice had reduced reproductive efficiency, sperm count, and abnormal sperm motility, with defects in the mitochondrial sheath structure, indicating Klc3's role in spermiogenesis [2].

In conclusion, Klc3 plays essential roles in sperm tail midpiece formation during spermiogenesis and in regulating ciliary trafficking in the context of CILK1-deficiency-related polycystic kidney disease. Mouse models, such as the Cilk1-deficient and spermatid-specific Klc3 mutant models, have been crucial in revealing these functions, providing insights into the molecular mechanisms underlying these biological processes and related diseases.

References:

1. Rah, Gyuyeong, Cha, Hwayeon, Kim, Joohee, Ko, Je Yeong, Park, Jong Hoon. 2022. KLC3 Regulates Ciliary Trafficking and Cyst Progression in CILK1 Deficiency-Related Polycystic Kidney Disease. In Journal of the American Society of Nephrology : JASN, 33, 1726-1741. doi:10.1681/ASN.2021111455. https://pubmed.ncbi.nlm.nih.gov/35961787/

2. Zhang, Ying, Ou, Young, Cheng, Min, Thundathil, Jacob C, van der Hoorn, Frans A. 2012. KLC3 is involved in sperm tail midpiece formation and sperm function. In Developmental biology, 366, 101-10. doi:10.1016/j.ydbio.2012.04.026. https://pubmed.ncbi.nlm.nih.gov/22561200/

3. Ma, Dan-Dan, Wang, Da-Hui, Yang, Wan-Xi. . Kinesins in spermatogenesis. In Biology of reproduction, 96, 267-276. doi:10.1095/biolreprod.116.144113. https://pubmed.ncbi.nlm.nih.gov/28203733/

4. Junco, A, Bhullar, B, Tarnasky, H A, van der Hoorn, F A. . Kinesin light-chain KLC3 expression in testis is restricted to spermatids. In Biology of reproduction, 64, 1320-30. doi:. https://pubmed.ncbi.nlm.nih.gov/11319135/

5. Zhang, Ying, Oko, Richard, van der Hoorn, Frans A. . Rat kinesin light chain 3 associates with spermatid mitochondria. In Developmental biology, 275, 23-33. doi:. https://pubmed.ncbi.nlm.nih.gov/15464570/