The transmembrane protein p23 contributes to the organization of the Golgi apparatus

Abstract

In previous studies we have shown that p23, a member of the p24-family of small transmembrane proteins, is highly abundant in membranes of the cis-Golgi network (CGN), and is involved in sorting/trafficking in the early secretory pathway. In the present study, we have further investigated the role of p23 after ectopic expression. We found that ectopically expressed p23 folded and oligomerized properly, even after overexpression. However, in contrast to endogenous p23, exogenous p23 molecules did not localize to the CGN, but induced a significant expansion of characteristic smooth ER membranes, where they accumulated in high amounts. This ER-derived, p23-rich subdomain displayed a highly regular morphology, consisting of tubules and/or cisternae of constant diameter, which were reminiscent of the CGN membranes containing p23 in control cells. The expression of exogenous p23 also led to the specific relocalization of endogenous p23, but not of other proteins, to these specialized ER-derived membranes. Relocalization of p23 modified the ultrastructure of the CGN and Golgi membranes, but did not affect anterograde and retrograde transport reactions to any significant extent. We conclude (i) that p23 has a morphogenic activity that contributes to the morphology of CGN-membranes; and (ii) that the presence of p23 in the CGN is necessary for the proper organization of the Golgi apparatus.

p24–Tango1 interactions ensure ER–Golgi interface stability and efficient transport

“…Furthermore, defective function of p24 proteins is associated with Alzheimer’s disease as mediators of amyloid precursor protein trafficking modulating γ-secretase cleavage ( Chen et al, 2006 ; Hasegawa et al, 2010 ; Vetrivel et al, 2007 ). Nevertheless, along with reports of defects in the transport of specific cargoes, evidence of more general impairments upon p24 deficiencies exists in the literature as well, such as altered Golgi–ER retrograde transport ( Aguilera-Romero et al, 2008 ; Gommel et al, 2001 ; Majoul et al, 1998 ; Montesinos et al, 2014 ) and abnormal Golgi morphology ( D’Arcangelo et al, 2015 ; Denzel et al, 2000 ; Koegler et al, 2010 ; Lavoie et al, 1999 ; Mitrovic et al, 2008 ; Pastor-Cantizano et al, 2018 ; Rojo et al, 2000 ). Moreover, broad roles have been ascribed to p24 proteins in mediating ER retention for quality control ( Belden and Barlowe, 2001 ; Dvela-Levitt et al, 2019 ; Gomez-Navarro et al, 2020 ; Lopez et al, 2020 ; Ma et al, 2017 ; Springer et al, 2000 ; Wen and Greenwald, 1999 ), membrane contact during autophagosome formation from the ERGIC (ER Golgi intermediate compartment) ( Li et al, 2022 ), and lipid transfer between the ER and Golgi ( Anwar et al, 2022 ).…”

p24-Tango1 interactions ensure ER-Golgi interface stability and efficient transport

“…Furthermore, defective function of p24 proteins is associated with Alzheimer’s disease as mediators of APP trafficking modulating γ-secretase cleavage (Chen et al, 2006; Hasegawa et al, 2010; Vetrivel et al, 2007). Nevertheless, along with reports of defects in the transport of specific cargos, evidence of more general impairments upon p24 deficiencies exist in the literature as well, such as altered Golgi-ER retrograde transport (Aguilera-Romero et al, 2008; Gommel et al, 2001; Majoul et al, 1998; Montesinos et al, 2014) and abnormal Golgi morphology (D’Arcangelo et al, 2015; Denzel et al, 2000; Koegler et al, 2010; Lavoie et al, 1999; Mitrovic et al, 2008; Pastor-Cantizano et al, 2018; Rojo et al, 2000). Moreover, broad roles have been ascribed to p24 proteins in mediating ER retention for quality control (Belden and Barlowe, 2001; Dvela-Levitt et al, 2019; Gomez-Navarro et al, 2020; Lopez et al, 2020; Ma et al, 2017; Springer et al, 2000; Wen and Greenwald, 1999), membrane contact during autophagosome formation from the ERGIC (ER Golgi Intermediate Compartment) (Li et al, 2022) and lipid transfer between the ER and Golgi (Anwar et al, 2022).…”

“…Furthermore, defective function of p24 proteins is associated with Alzheimer's disease as mediators of APP trafficking modulating γ-secretase cleavage (Chen et al, 2006;Hasegawa et al, 2010;Vetrivel et al, 2007). Nevertheless, along with reports of defects in the transport of specific cargos, evidence of more general impairments upon p24 deficiencies exist in the literature as well, such as altered Golgi-ER retrograde transport (Aguilera-Romero et al, 2008;Gommel et al, 2001;Majoul et al, 1998;Montesinos et al, 2014) and abnormal Golgi morphology (D'Arcangelo et al, 2015;Denzel et al, 2000;Koegler et al, 2010;Lavoie et al, 1999;Mitrovic et al, 2008;Pastor-Cantizano et al, 2018;Rojo et al, 2000).…”