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. 2021 Mar 5;13(1):56–76. doi: 10.1080/21541248.2021.1892443

Figure 10.

Figure 10.

The proposed function models of the C9orf72-SMCR8-WDR41 complex.

a. The C9orf72-SMCR8-WDR41 complex acts as the GAP for ARF1 or other small GTPases in the cytoplasm, whereas the C9orf72-SMCR8-WDR41 complex cannot function as the GAP of ARF1 when it is sequestered by SLC66A1/PQLC2, which can sense the level of cationic amino acids and binds to WDR41 at the inwards open conformation. On the other hand, recruitment of the CSW complex to the lysosome is essential to the cross-talk between the CSW complex and its partners on the lysosome. The structure model of SLC66A1/PQLC2 is generated using human SLC26A9 (PDB:7CH1) as a template [183]. Grey: ARF1, orange, and teal: SLC66A1/PQLC2. Blue: C9orf72, pink: SMCR8, green: WDR41, grey: RABs. The arrows with a solid line indicate reported signal pathways, whereas the arrows with a dashed line indicate proposed connections.

b. Model of the CSW complex localizing on ER or Golgi apparatus: the CSW complex localizes on ER/Golgi via binding to receptors or lipidation. The labels and colours are the same as the panel(A). The brown lines with a circle head denote the lipidation.

C. The C9orf72-SMCR8-WDR41 complex tether two endosomes/vesicles and regulates the fusion through its GAP activity. The C9orf72-SMCR8-WDR41 complex is coloured as a panel(A).