Exoc2-flox Mouse

EXOC2, also known as Sec5, encodes an essential subunit of the exocyst complex. The exocyst is an octameric protein complex crucial for the membrane transport machinery, specifically for tethering and fusion of vesicles at the plasma membrane [2]. It is involved in various cellular processes like exocytosis, vesicle fusion, and contributes to normal cellular function and development [2]. Genetic models, such as knockout models, can be valuable to study its functions.

In C9ORF72-ALS/FTD patients, deleting EXOC2 in induced pluripotent stem cells (iPSCs) rescued several disease-relevant cellular phenotypes in iPSC-derived motor neurons. This was due to decreased levels of dipeptide repeat (DPR) proteins and expanded G4C2 repeats-containing RNA. Treatment with EXOC2 antisense oligonucleotides in fully differentiated neurons had similar effects, suggesting EXOC2 is a potential therapeutic target [1].

In human brain development, pathogenic variants in EXOC2 led to severe developmental delay, dysmorphism, brain abnormalities, and defective Arl13b localization to the primary cilium, indicating its importance in neural development [2].

In the context of infections, EXOC2 is involved in Salmonella invasion as the bacteria recruit exocyst subunits including EXOC2 from membrane reservoirs for invasion ruffle formation [3]. It's also a potential host factor for SARS-CoV-2 infection, as EXOC2 knockdown decreased intracellular virus nucleocapsid expression and virus copy number [4].

In conclusion, EXOC2 plays essential roles in multiple biological processes, including membrane transport, neural development, and is implicated in various disease conditions such as ALS/FTD, severe brain development defects, and viral and bacterial infections. The use of genetic models, like those in the studies of EXOC2 in ALS/FTD, has provided valuable insights into its function in disease, highlighting its potential as a therapeutic target in these areas.