Snx27-flox Mouse

Snx27 belongs to the sorting nexin (SNX) family of proteins. It is unique in containing both a Phox (PX) domain and an additional PDZ domain. Snx27 plays a critical role in protein sorting and trafficking in the endocytosis pathway, mediating the recycling of internalized proteins from endosomes to the plasma membrane in a PDZ domain-dependent manner. It is associated with the retromer complex and is involved in multiple cellular functions, which are essential for normal cellular function and preventing human diseases [1,3].

In T-cell activation, Snx27 translocates to the T cell-APC interface upon TCR activation, facilitating the transport of cargoes and interacting with DGKζ to sustain DAG modulation for IS organization and signaling [2]. In viral infections, Snx27 together with the retromer complex prevents the ACE2/virus complex from entering lysosome/late endosome, decreasing SARS-CoV-2 viral entry [4]. In cytomegalovirus replication, Snx27:Retromer:ESCPE-1-mediated tubulation is essential for the establishment of a Rab10-decorated subset of membranes within the pre-AC, and suppression of Snx27-mediated functions leads to a decrease in infectious virion release [7]. In neurological function, Snx27-mediated recycling of neuroligin-2 regulates inhibitory signaling by enhancing synaptic neuroligin-2 clusters [8]. In cancer, while its role in tumorigenesis is not fully understood, its over-expression is linked to tumorigenesis, cancer progression, and metastasis. For example, circ_Snx27 in hepatocellular carcinoma promotes cancer development via the miR-637/FGFR1 axis and circ-Snx27 sponging miR-375/RPN1 axis contributes to HCC progression [5,6]. Also, Snx27 inhibits TNFα-induced NF-κB signalling activation by facilitating OTULIN to localize to TNF receptor complex [9].

In conclusion, Snx27 is crucial for endosomal protein recycling and has diverse functions in various biological processes and diseases. Its role in T-cell activation, viral infections, cytomegalovirus replication, neurological function, and cancer development has been revealed through different studies. Understanding Snx27's functions provides insights into normal cellular function and offers potential strategies for treating related diseases.