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Review
. 2018 Nov 28;38(24):e00446-18.
doi: 10.1128/MCB.00446-18. Print 2018 Dec 15.

New Player in Endosomal Trafficking: Differential Roles of Smad Anchor for Receptor Activation (SARA) Protein

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Free PMC article
Review

New Player in Endosomal Trafficking: Differential Roles of Smad Anchor for Receptor Activation (SARA) Protein

Victoria Rozés-Salvador et al. Mol Cell Biol. .
Free PMC article

Abstract

The development and maintenance of multicellular organisms require specialized coordination between external cellular signals and the proteins receiving stimuli and regulating responses. A critical role in the proper functioning of these processes is played by endosomal trafficking, which enables the transport of proteins to targeted sites as well as their return to the plasma membrane through its essential components, the endosomes. During this trafficking, signaling pathways controlling functions related to the endosomal system are activated both directly and indirectly. Although there are a considerable number of molecules participating in these processes, some are more known than others for their specific functions. Toward the end of the 1990s, Smad anchor for receptor activation (SARA) protein was described to be controlling and to facilitate the localization of Smads to transforming growth factor β (TGF-β) receptors during TGF-β signaling activation, and, strikingly, SARA was also identified to be one of the proteins that bind to early endosomes (EEs) participating in membrane trafficking in several cell models. The purpose of this review is to analyze the state of the art of the contribution of SARA in different cell types and cellular contexts, focusing on the biological role of SARA in two main processes, trafficking and cellular signaling, both of which are necessary for intercellular coordination, communication, and development.

Keywords: SARA; TGF-β; development; endosomal trafficking; signaling.

Figures

FIG 1
FIG 1
Representative image of the SARA isoforms (SARA1 and SARA2) present in mouse with their domains and sites of interaction with different proteins, such as Smad2/3, PP1c, and TβRI. aa, amino acid.
FIG 2
FIG 2
Representative image of the participation of SARA in the TGF-β signaling pathway. Once the receptor complex has been endocytosed with the TGF-β ligand, SARA binds to TβRI and recruits Smad2/3, and this is phosphorylated. Then, Smad2/3 binds to Smad4, and together they translocate to the nucleus and modulate the expression of target genes. On the other hand, the complex formed by Smad7-GADD34-PP1c acts as a negative regulator of the route, dephosphorylating TβRI.

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