Fez1, also known as Fasciculation and elongation protein zeta-1, is a multifunctional kinesin adaptor. It is involved in a wide range of biological processes, including neurodegeneration, viral infection, and cell proliferation and differentiation. It plays a role in the regulation of interferon-stimulated gene (ISG) expression, interacts with proteins like HSPA8 to control its nuclear-cytoplasmic localization [1]. It is also part of pathways related to axon and dendrite development in neurons, and may be involved in tumourigenesis, as it has been proposed as a candidate tumour suppressor gene [5,6]. Genetic models such as gene knockout (KO) or conditional knockout (CKO) mouse models can be valuable for studying Fez1's functions in vivo.

In Fez1-null human cerebral organoids, there is abnormal expansion of certain neuronal progenitor subpopulations and disruption of cortical layer formation, highlighting its role in early cortical brain development [4]. Knocking down Fez1 in corneal epithelial cells reduces cell division and causes cell cycle arrest, suggesting its importance in corneal epithelial cell proliferation [2]. In early HIV-1 infection, depletion of Fez1 reduces the accumulation of fused HIV-1 particles around the nucleus and suppresses infection, indicating its role in viral trafficking [3].

In conclusion, Fez1 is essential for multiple biological processes. Model-based research, especially KO/CKO mouse models, has revealed its significance in neurodevelopment, cell proliferation, and viral infection. These findings contribute to our understanding of related diseases, such as neurodevelopmental disorders and viral infections, and may provide potential therapeutic targets.

References:

1. Malikov, Viacheslav, Meade, Nathan, Simons, Lacy M, Hultquist, Judd F, Naghavi, Mojgan H. . FEZ1 phosphorylation regulates HSPA8 localization and interferon-stimulated gene expression. In Cell reports, 38, 110396. doi:10.1016/j.celrep.2022.110396. https://pubmed.ncbi.nlm.nih.gov/35172151/

2. Zhu, Liqiong, Wang, Li, Liu, Dongmei, Yuan, Jin, Ouyang, Hong. 2023. Single-cell transcriptomics implicates the FEZ1-DKK1 axis in the regulation of corneal epithelial cell proliferation and senescence. In Cell proliferation, 56, e13433. doi:10.1111/cpr.13433. https://pubmed.ncbi.nlm.nih.gov/36851859/

3. Malikov, Viacheslav, Naghavi, Mojgan H. 2023. FEZ1 Plays Dual Roles in Early HIV-1 Infection by Independently Regulating Capsid Transport and Host Interferon-Stimulated Gene Expression. In Journal of virology, 97, e0049923. doi:10.1128/jvi.00499-23. https://pubmed.ncbi.nlm.nih.gov/37219433/

4. Qu, Yinghua, Lim, Jonathan Jun-Yong, An, Omer, Toh, Yi-Chin, Chua, John Jia En. 2023. FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations. In iScience, 26, 108497. doi:10.1016/j.isci.2023.108497. https://pubmed.ncbi.nlm.nih.gov/38213789/

5. Chua, Jie Yin, Ng, Shi Jun, Yagensky, Oleksandr, Wanker, Erich E, Chua, John Jia En. 2021. FEZ1 Forms Complexes with CRMP1 and DCC to Regulate Axon and Dendrite Development. In eNeuro, 8, . doi:10.1523/ENEURO.0193-20.2021. https://pubmed.ncbi.nlm.nih.gov/33771901/

6. Califano, Daniela, Pignata, Sandro, Pisano, Carmela, Fusco, Alfredo, Chiappetta, Gennaro. . FEZ1/LZTS1 protein expression in ovarian cancer. In Journal of cellular physiology, 222, 382-6. doi:10.1002/jcp.21962. https://pubmed.ncbi.nlm.nih.gov/19885841/