The DrosophilaSTIM1 orthologue, dSTIM, has roles in cell fate specification and tissue patterning

Jean-Pierre Eid,Hannah Robertson,Gary R Hime,Marie Dziadek,Alfonso Martinez Arias

doi:10.1186/1471-213x-8-104

Abstract

BackgroundMammalian STIM1 and STIM2 and the single Drosophila homologue dSTIM have been identified as key regulators of store-operated Ca2+ entry in cells. STIM proteins function both as molecular sensors of Ca2+concentration in the endoplasmic reticulum (ER) and the molecular triggers that activate SOC channels in the plasma membrane. Ca2+ is a crucial intracellular messenger utilised in many cellular processes, and regulators of Ca2+ homeostasis in the ER and cytosol are likely to play important roles in developmental processes. STIM protein expression is altered in several tumour types but the role of these proteins in developmental signalling pathways has not been thoroughly examined.ResultsWe have investigated the expression and developmental function of dSTIM in Drosophila and shown that dSTIM is widely expressed in embryonic and larval tissues. Using the UAS-Gal4 induction system, we have expressed full-length dSTIM protein and a dsRNAi construct in different tissues. We demonstrate an essential role for dSTIM in larval development and survival, and a tissue-specific role in specification of mechanosensory bristles in the notum and specification of wing vein thickness.ConclusionOur studies show that dSTIM regulates growth and patterning of imaginal discs and indicate potential interactions with the Notch and Wingless signaling pathways. These interactions may be relevant to studies implicating STIM family proteins in tumorigenesis.

Highlights

Mammalian STIM1 and STIM2 and the single Drosophila homologue dSTIM have been identified as key regulators of store-operated Ca2+ entry in cells
Results dSTIM expression in early Drosophila embryos To detect dSTIM RNA expression during embryonic development we performed whole mount in situ hybridization using DIG-labelled RNA probes (Fig. 1A–K). dSTIM RNA was maternally deposited in the Drosophila egg (Fig. 1A), with transcript levels decreasing as development proceeded through stages of early nuclear division, pole cell formation, syncytial blastoderm and cellularisation (Fig. 1A–C). dSTIM transcripts appeared to be excluded from pole cells (Fig. 1B, C)
Our results suggest that Notch and dSTIM may intersect at a functional level through activation of calcineurin independently of NFATc proteins in Drosophila, and further studies are required to elucidate the molecular nature of these interactions

Summary

Introduction

Mammalian STIM1 and STIM2 and the single Drosophila homologue dSTIM have been identified as key regulators of store-operated Ca2+ entry in cells. Ca2+ is a crucial intracellular messenger utilised in many cellular processes, and regulators of Ca2+ homeostasis in the ER and cytosol are likely to play important roles in developmental processes. Since changes in cytosolic Ca2+ trigger calcium-dependent cellular responses by activating signaling and transcriptional cascades mediated by Ca2+dependent proteins [3,4], the levels of cytosolic Ca2+ need to be highly regulated to effect appropriate developmental signaling responses. The developmental regulation of the Ca2+ flux between the ER lumen and the cytosol, and the replenishment of Ca2+ stores from extracellular Ca2+ is likely to play a significant role in the signaling pathways that specify changes in cell phenotype

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