The Golgin GMAP210/TRIP11 Anchors IFT20 to the Golgi Complex

Abstract

Eukaryotic cells often use proteins localized to the ciliary membrane to monitor the extracellular environment. The mechanism by which proteins are sorted, specifically to this subdomain of the plasma membrane, is almost completely unknown. Previously, we showed that the IFT20 subunit of the intraflagellar transport particle is localized to the Golgi complex, in addition to the cilium and centrosome, and hypothesized that the Golgi pool of IFT20 plays a role in sorting proteins to the ciliary membrane. Here, we show that IFT20 is anchored to the Golgi complex by the golgin protein GMAP210/Trip11. Mice lacking GMAP210 die at birth with a pleiotropic phenotype that includes growth restriction, ventricular septal defects of the heart, omphalocele, and lung hypoplasia. Cells lacking GMAP210 have normal Golgi structure, but IFT20 is no longer localized to this organelle. GMAP210 is not absolutely required for ciliary assembly, but cilia on GMAP210 mutant cells are shorter than normal and have reduced amounts of the membrane protein polycystin-2 localized to them. This work suggests that GMAP210 and IFT20 function together at the Golgi in the sorting or transport of proteins destined for the ciliary membrane.

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

“…Compared with other IFT-B proteins, IFT20 has an unusual distribution. In addition to being found in both primary cilia and the centrosome pool, it is present in the Golgi apparatus (40). This finding raises the possibility that IFT20 might participate in intracellular membrane trafficking, in addition to its role in ciliary assembly.…”

“…The golgin GMAP210/TRIP11 anchors IFT20 to the Golgi complex, and both molecules function together in the trafficking of ciliary membrane proteins (40). An initial report suggests that loss of GMAP210/TRIP11 in mice alters glycosylation in the Golgi, leading to the intracellular accumulation of Perlecan in chondrocytes and resulting in a neonatal lethal form of skeletal dysplasia (57).…”

Cilia and coordination of signaling networks during heart development

“…20,146 In support of a critical role of cilia in heart development, mutations in genes involved in trafficking of vesicles to and from the cilium are associated with CHD. Mutant mouse embryos lacking the Golgi-associated protein, Gmap210, which is required for Ift20-mediated trafficking and localization of PC2 to the cilium, 147 die around the time of birth and show heart defects including VSD and TOF. 147 In agreement with this, Pkd2 −/− mouse embryos display heart defects reminiscent of those observed in Gmap210 −/− mouse embryos.…”

“…Mutant mouse embryos lacking the Golgi-associated protein, Gmap210, which is required for Ift20-mediated trafficking and localization of PC2 to the cilium, 147 die around the time of birth and show heart defects including VSD and TOF. 147 In agreement with this, Pkd2 −/− mouse embryos display heart defects reminiscent of those observed in Gmap210 −/− mouse embryos. 148 Further, Pifo −/− E7.5 mouse embryos, which lack Pitchfork that interacts with components of the endocytic machinery, including the small GTPases Rab8, Rab11 and Arl13b, and induces the resorption of the primary cilium before entry into mitosis, 19 display double-ciliated cells in the nodal pit as well as L-R defects with associated cardiac defects, including DORV and right ventricle hypoplasia.…”

Role of the MAPK/cJun NH 2 -terminal kinase signaling pathway in starvation-induced autophagy

“…Kidneys were digested (2 h) with 0.1% collagenase A (Millipore Sigma, 11,088,793,001) plus 0.1% trypsin (Thermo Fisher Scientific, 15,090,046) in DMEM with 150 mM NaCl [56]. The cells were maintained in DMEM/F-12 media (Thermo Fisher Scientific, 11,039–047) containing 10% BGS, plus 150 mM urea and 150 mM NaCl.…”