Bet1-KO Mouse

Bet1 is a gene that, along with its SNARE complex partners GOSR2, SEC22b, and Syntaxin-5, is essential for the fusion of endoplasmic reticulum-derived vesicles with the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, thus playing a crucial role in the ER-to-Golgi transport pathway [1,3,4,5]. Genetic models, such as yeast models, have been valuable in studying its function [2,3].

In humans, biallelic variants in BET1 have been found in three individuals from two families with severe congenital muscular dystrophy (CMD) and epilepsy. The variants led to low BET1 protein levels, impaired ER-to-Golgi transport, and mislocalization of ERGIC-53 in fibroblasts, establishing BET1 as a novel CMD/epilepsy gene [1]. In cancer research, MT1-MMP recruits Bet1 to promote its trafficking to the cell surface, likely to invadopodia, suggesting Bet1's role in cancer metastasis [4].

In conclusion, Bet1 is essential for ER-to-Golgi vesicular transport. Studies on Bet1, especially through genetic models in disease-related contexts, have revealed its significance in conditions like CMD with epilepsy and potentially in cancer metastasis, highlighting its importance in understanding the underlying biological mechanisms and developing related therapies.

References:

1. Donkervoort, Sandra, Krause, Niklas, Dergai, Mykola, Bönnemann, Carsten G, Schwake, Michael. 2021. BET1 variants establish impaired vesicular transport as a cause for muscular dystrophy with epilepsy. In EMBO molecular medicine, 13, e13787. doi:10.15252/emmm.202013787. https://pubmed.ncbi.nlm.nih.gov/34779586/

2. Ferro-Novick, S, Newman, A P, Groesch, M, Graf, J, Shim, J. . An analysis of BET1, BET2, and BOS1. Three factors mediating ER to Golgi transport in yeast. In Cell biophysics, 19, 25-33. doi:. https://pubmed.ncbi.nlm.nih.gov/1726885/

3. Newman, A P, Shim, J, Ferro-Novick, S. . BET1, BOS1, and SEC22 are members of a group of interacting yeast genes required for transport from the endoplasmic reticulum to the Golgi complex. In Molecular and cellular biology, 10, 3405-14. doi:. https://pubmed.ncbi.nlm.nih.gov/2192256/

4. Miyagawa, Takuya, Hasegawa, Kana, Aoki, Yoko, Tagaya, Mitsuo, Inoue, Hiroki. 2019. MT1-MMP recruits the ER-Golgi SNARE Bet1 for efficient MT1-MMP transport to the plasma membrane. In The Journal of cell biology, 218, 3355-3371. doi:10.1083/jcb.201808149. https://pubmed.ncbi.nlm.nih.gov/31519727/

5. Bravo-Plaza, Ignacio, Tagua, Victor G, Arst, Herbert N, Galindo, Antonio, Peñalva, Miguel A. 2023. The Uso1 globular head interacts with SNAREs to maintain viability even in the absence of the coiled-coil domain. In eLife, 12, . doi:10.7554/eLife.85079. https://pubmed.ncbi.nlm.nih.gov/37249218/