Coronin 7, the mammalian POD‐1 homologue, localizes to the Golgi apparatus

Abstract

Coronins constitute an evolutionary conserved family of WD-repeat actin-binding proteins. Their primary function is thought to be regulating the actin cytoskeleton. Apart from that, several coronins were indirectly shown to participate in vesicular transport, establishment of cell polarity and cytokinesis. Here, we report a novel mammalian protein, coronin 7 (crn7), which is significantly different from other mammalian coronins in its domain architecture. Crn7 possesses two stretches of WD repeats in contrast to the other coronins only having one. The protein is expressed throughout the mouse embryogenesis and is strongly upregulated in brain and developing structures of the immune system in the course of development. In adult animals, both crn7 mRNA and protein are abundantly present in most organs, with significantly higher amounts in brain, kidney, thymus and spleen and lower amounts in muscle. At the subcellular level, the bulk of the protein appears to be present in the cytosol and in large cytosolic complexes. However, a significant portion of the protein is detected on vesicle-like cytoplasmic structures as well as on the cis-Golgi. In the Golgi region, crn7 staining appears broader than that of the cis-Golgi markers Erd2p and b-COP, still, the trans-Golgi network appears predominantly crn7-negative. Importantly, the membrane-associated form of crn7 protein is phosphorylated on tyrosine residues, whereas the cytosolic form is not. Crn7 is the first coronin protein proven to localize to the Golgi membrane. We conclude that it plays a role in the organization of intracellular membrane compartments and vesicular trafficking rather than in remodeling the cytoskeleton.

Actin acting at the Golgi

“…602 Very little is known about the Golgi and actin cytoskeleton 603 interaction in this organism, but consistent with a possible 604 role of coronin 7 in Golgi trafficking (Rybakin et al 2004;605 Rybakin and Clemen 2005), depletion of the coronin 7 606 homolog POD1 leads to aberrant accumulation of vesicles 607 in cells of the early embryo (Rappleye et al 1999). 608 Moreover, CRP-1, a Cdc42-related protein, localizes at the 609 TGN and recycling endosomes.…”

Coronin7 forms a novel E3 ubiquitin ligase complex to promote the degradation of the anti-proliferative protein Tob

“…It is possible that the N-terminal half of CRN7 has a negative effect on Tob degradation and that a conformational change in CRN7 in response to cellular signaling modulates the activity. CRN7 is known to participate in the regulation of Golgi trafficking [18,19]; however, its involvement in proteosome-mediated degradation has not been reported. We show here for the first time that CRN7 forms a novel E3 ligase complex.…”

“…Since CRN7 is strongly expressed in the cells and tissues of the immune system, such as the thymus, in both human and mice ( Fig. 1) [18], and since Tob is involved in T-cell responses [26], it would be interesting to investigate the biological significance of CRN7-mediated Tob degradation on immune function.…”

“…Unlike the other coronin family members which contain a single cluster of WD repeats, CRN7 contains two clusters of WD repeat motifs. CRN7 is localized mainly in the cytoplasm and the Golgi apparatus [18]. RNA interference-mediated inhibition of CRN7 results in morphological changes in the Golgi apparatus and the subsequent disruption of anterograde Golgi-to-plasma membrane transport [19].…”

“…RNA interference-mediated inhibition of CRN7 results in morphological changes in the Golgi apparatus and the subsequent disruption of anterograde Golgi-to-plasma membrane transport [19]. Since CRN7 interacts with the clathrin adaptor AP-1, the function of CRN7 may be important for clathrin-dependent membrane trafficking [18,19].…”