ABCC5 is required for cAMP-mediated hindgut invagination in sea urchin embryos

Abstract

ATP-binding cassette (ABC) transporters are evolutionarily conserved proteins that pump diverse substrates across membranes. Many are known to efflux signaling molecules and are extensively expressed during development. However, the role of transporters in moving extracellular signals that regulate embryogenesis is largely unexplored. Here, we show that a mesodermal ABCC (MRP) transporter is necessary for endodermal gut morphogenesis in sea urchin embryos. This transporter, Sp-ABCC5a (C5a), is expressed in pigment cells and their precursors, which are a subset of the non-skeletogenic mesoderm (NSM) cells. C5a expression depends on Delta/Notch signaling from skeletogenic mesoderm and is downstream of Gcm in the aboral NSM gene regulatory network. Long-term imaging of development reveals that C5a knockdown embryos gastrulate, but ∼90% develop a prolapse of the hindgut by the late prism stage (∼8 h after C5a protein expression normally peaks). Since C5a orthologs efflux cyclic nucleotides, and cAMP-dependent protein kinase (Sp-CAPK/PKA) is expressed in pigment cells, we examined whether C5a could be involved in gastrulation through cAMP transport. Consistent with this hypothesis, membrane-permeable pCPT-cAMP rescues the prolapse phenotype in C5a knockdown embryos, and causes archenteron hyper-invagination in control embryos. In addition, the cAMP-producing enzyme soluble adenylyl cyclase (sAC) is expressed in pigment cells, and its inhibition impairs gastrulation. Together, our data support a model in which C5a transports sAC-derived cAMP from pigment cells to control late invagination of the hindgut. Little is known about the ancestral functions of ABCC5/MRP5 transporters, and this study reveals a novel role for these proteins in mesoderm-endoderm signaling during embryogenesis.

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis

“… 33 , 34 Furthermore, as with other oesophageal adenocarcinoma genes implicated by genome-wide association studies (eg, FOXF1 and FOXP1 ), 7 , 9 ABCC5 has a role during embryonal development of the intestine. 35 Apart from the exact functional role of rs9823696, markers that contribute solely to oesophageal adenocarcinoma development could serve as predictors for disease progression in Barrett's oesophagus. Because Barrett's oesophagus is common in the population and only a few patients develop oesophageal adenocarcinoma, specific markers for the transition of Barrett's oesophagus to oesophageal adenocarcinoma are needed.…”

Transporter-interfering chemicals inhibit P-glycoprotein of yellowfin tuna (Thunnus albacares)

“…To validate transporter localization and efflux activity in a marine cell, we used a well-established transporter overexpression method in purple sea urchin embryos (Gokirmak et al, 2016;Gökirmak et al, 2014Gökirmak et al, , 2012Shipp et al, 2015). In this assay the mRNA encoding the transporter fused to a fluorescent protein reporter is injected into sea urchin embryos.…”

Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

“…These small molecule transporters (SMTs) are expressed at environmental barriers such as the epithelial cells lining the gut, where they can export toxic compounds for excretion [9,10]. They are also highly expressed in stem cells and embryos [11][12][13][14][15][16][17].…”