Nbr1-KO Mouse

Nbr1, the NBR1 autophagy cargo receptor, is a key player in selective autophagy. It was discovered soon after the vertebrate autophagy receptor p62/SQSTM1. Evolutionary analysis shows Nbr1 likely existed in the last eukaryotic common ancestor, and yeast-selective autophagy receptors Atg19 and Atg34 are its homologs. Nbr1 is the main autophagy receptor in plants lacking p62, while most animals have both Nbr1 and p62. It's involved in the autophagic degradation of protein aggregates in mammals, with several of its domains contributing to cargo recognition [1].

In breast cancer, genetic autophagy inhibition leads to cytosolic accumulation of Nbr1 in autophagy-deficient tumor cells, paradoxically promoting metastasis, indicating that autophagy suppresses breast cancer metastasis by degrading Nbr1 [2]. In plants, Nbr1-mediated selective autophagy is crucial for various stress responses. For example, in Arabidopsis, Nbr1 plays a role in regulating heat stress memory by targeting HSP90.1 and ROF1 for autophagic degradation, and loss-of-function mutation of Nbr1 results in a stronger heat stress memory phenotype [3]. In enteric coronavirus infection, the viral nsp2 recruits Nbr1 for autophagic targeting of TBK1, diminishing the innate immune response, and the replication of the nsp2-deficient virus is restrained by reduced autophagy [4].

In conclusion, Nbr1 is essential for selective autophagy and has diverse functions. In cancer, especially breast cancer, its regulation by autophagy is linked to metastasis. In plants, it is vital for stress responses like heat stress memory. In viral infections, it can be exploited by viruses to evade the immune system. The study of Nbr1 through genetic models such as knockout or conditional knockout mouse models (if applicable in the respective studies) has provided insights into these biological processes and disease-related mechanisms.

References:

1. Rasmussen, Nikoline Lander, Kournoutis, Athanasios, Lamark, Trond, Johansen, Terje. 2022. NBR1: The archetypal selective autophagy receptor. In The Journal of cell biology, 221, . doi:10.1083/jcb.202208092. https://pubmed.ncbi.nlm.nih.gov/36255390/

2. Marsh, Timothy, Debnath, Jayanta. 2020. Autophagy suppresses breast cancer metastasis by degrading NBR1. In Autophagy, 16, 1164-1165. doi:10.1080/15548627.2020.1753001. https://pubmed.ncbi.nlm.nih.gov/32267786/

3. Thirumalaikumar, Venkatesh P, Gorka, Michal, Schulz, Karina, Vierstra, Richard D, Balazadeh, Salma. 2020. Selective autophagy regulates heat stress memory in Arabidopsis by NBR1-mediated targeting of HSP90.1 and ROF1. In Autophagy, 17, 2184-2199. doi:10.1080/15548627.2020.1820778. https://pubmed.ncbi.nlm.nih.gov/32967551/

4. Jiao, Yajuan, Zhao, Pengwei, Xu, Ling-Dong, Wang, Bin, Huang, Yao-Wei. 2024. Enteric coronavirus nsp2 is a virulence determinant that recruits NBR1 for autophagic targeting of TBK1 to diminish the innate immune response. In Autophagy, 20, 1762-1779. doi:10.1080/15548627.2024.2340420. https://pubmed.ncbi.nlm.nih.gov/38597182/