Fig 2: A working model on Rab11-FIP1- and Rab11-FIP5-mediated pIgA transcytosis in incompletely polarized cells. In our incompletely polarized cells model, pIgA is recognized and bound by pIgR upon pIgA treatment. Subsequently, the endocytic pIgR–pIgA complex is delivered by Rab11a-positive endosomes. The complex is first transported from the basolateral plasma membrane to the vicinity of the centrosome where Rab11-FIP1 and Rab11-FIP5 bind to it. During the trafficking process, TRIM21 mediates the K11-linked polyubiquitination of Rab11-FIP1 and the K6-linked polyubiquitination of Rab11-FIP5 to promote their activation. With the assistance of Rab11-FIP1 and Rab11-FIP5, pIgR–pIgA complex is further transferred to the apical plasma membrane via Golgi apparatus and then secreted.

Fig 3: The effect of TBC1D23 and RAB11A interaction on NSCLC cells.(A) Scratch assay showing that TBC1D23 promoted the migration of NSCLC cells by interacting with RAB11A. Magnification ×100. (B) Transwell assay showing that TBC1D23 promoted the migration and invasion of NSCLC cells by interacting with RAB11A. Magnification ×200. (C) Western blot showing that TBC1D23 upregulated cyclin B1, cyclin D1, CDK2 and CDK6 to promote the proliferation of NSCLC cells and upregulated RhoA, RhoC and MMP2 to promote the migration and invasion of NSCLC cells by interacting with RAB11. *p < 0.05; **p < 0.01; ***p < 0.001. Data are presented as means ± SD (n = 3)

Fig 4: The effect of TBC1D23 on ß1-integrin. (A) Immunofluorescence showing that RAB11A and ß1 integrin could not bind in the para-nucleus when TBC1D23 is knocked down. Magnification ×400. (B)Immunofluorescence showing that RAB11A and ß1 integrin were bound in the para-nucleus after TBC1D23 was overexpressed in cells with TBC1D23 knocked down. Magnification ×400. (C) Immunohistochemistry showing that TBC1D23 was positively correlated with ß1-integrin expression. Magnification ×100 *p < 0.05; **p < 0.01; ***p < 0.001. Data are presented as means ± SD (n = 3)

Fig 5: The effect of TBC1D23 on the ß1-integrin/FAK/ERK signalling pathway. (A) Western blot showing that TBC1D23 could activate the ß1 integrin/FAK/ERK signalling pathway. (B) Western blot showing that TBC1D23 could activate the ß1-integrin/FAK/ERK signalling pathway by interacting with RAB11A. (C) Real-time PCR showing that TBC1D23 did not affect ß1-integrin mRNA expression. (D) In A549 cells, ß1-integrin expression on the cell membrane was determined by flow cytometry 0, 60 and 90 min after NZ washout. (E) Flow cytometry showing ß1-integrin expression on the cell membrane in experimental and control groups after NZ washout. The vertical axis of the bar chart shows an increase of 90 min over 60 min. *p < 0.05; **p < 0.01; ***p < 0.001. Data are presented as means ± SD (n = 3)