The <i>Drosophila</i> photoreceptor as a model system for studying signalling at membrane contact sites

Yadav, Shweta; Cockcroft, Shamshad; Raghu, Padinjat

doi:10.1042/bst20150256

Cited by 22 publications

(19 citation statements)

References 32 publications

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“…dPLD has been reported to be localized in the submicrovillar cisternae (LaLonde et al, 2005; Raghu et al, 2009), a specialization of the smooth endoplasmic reticulum that is positioned ca. 10 nm from the plasma membrane at the base of the microvilli (Yadav et al, 2016). At this location, dPLD might bind to the C-terminal tail of M either before or after it is endocytosed into RLV; binding of mammalian PLD1 has been reported to the C-terminal tail of several rhodopsin superfamily GPCRs including the 5-HT2 a , muscarinic and opioid receptors [(Barclay et al, 2011) and references therein].…”

Section: Discussionmentioning

confidence: 99%

Phospholipase D activity couples plasma membrane endocytosis with retromer dependent recycling

Thakur

Panda

Coessens

et al. 2016

eLife

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During illumination, the light-sensitive plasma membrane (rhabdomere) of Drosophila photoreceptors undergoes turnover with consequent changes in size and composition. However, the mechanism by which illumination is coupled to rhabdomere turnover remains unclear. We find that photoreceptors contain a light-dependent phospholipase D (PLD) activity. During illumination, loss of PLD resulted in an enhanced reduction in rhabdomere size, accumulation of Rab7 positive, rhodopsin1-containing vesicles (RLVs) in the cell body and reduced rhodopsin protein. These phenotypes were associated with reduced levels of phosphatidic acid, the product of PLD activity and were rescued by reconstitution with catalytically active PLD. In wild-type photoreceptors, during illumination, enhanced PLD activity was sufficient to clear RLVs from the cell body by a process dependent on Arf1-GTP levels and retromer complex function. Thus, during illumination, PLD activity couples endocytosis of RLVs with their recycling to the plasma membrane thus maintaining plasma membrane size and composition.DOI: http://dx.doi.org/10.7554/eLife.18515.001

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Section: Discussionmentioning

confidence: 99%

Phospholipase D activity couples plasma membrane endocytosis with retromer dependent recycling

Thakur

Panda

Coessens

et al. 2016

eLife

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“…RDGBα is a membrane-associated protein (Yadav et al, 2015) with a highly restricted localization within PRs (Suzuki and Hirosawa, 1994;Vihtelic et al, 1993). Endogenous RDGBα is present on submicrovillar cisternae (SMC), a specialized ER compartment near the base of the rhabdomeral PM, an arrangement reminiscent of an ER-PM membrane contact site (MCS) (Yadav et al, 2016). In a recent study, rdgB mutants were shown to have defects in PI and PA turnover following activation of PLC signalling (Yadav et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

RDGBα localization and function at membrane contact sites is regulated by FFAT–VAP interactions

Yadav

Thakur

Georgiev

et al. 2018

Journal of Cell Science

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Phosphatidylinositol transfer proteins (PITPs) are essential regulators of PLC signalling. The PI transfer domain (PITPd) of multi-domain PITPs is reported to be sufficient for function, questioning the relevance of other domains in the protein. In photoreceptors, loss of RDGBα, a multi-domain PITP localized to membrane contact sites (MCSs), results in multiple defects during PLC signalling. Here, we report that the PITPd of RDGBα does not localize to MCSs and fails to support function during strong PLC stimulation. We show that the MCS localization of RDGBα depends on the interaction of its FFAT motif with dVAP-A. Disruption of the FFAT motif (RDGB) or downregulation of dVAP-A, both result in mis-localization of RDGBα and are associated with loss of function. Importantly, the ability of the PITPd in full-length RDGB to rescue mutant phenotypes was significantly worse than that of the PITPd alone, indicating that an intact FFAT motif is necessary for PITPd activity Thus, the interaction between the FFAT motif and dVAP-A confers not only localization but also intramolecular regulation on lipid transfer by the PITPd of RDGBα. This article has an associated First Person interview with the first author of the paper.

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“…In contrast to mammalian tissue culture cells, in Drosophila photoreceptors, the single PITPNM is constitutively localized at the SMC a MCS between the ER and the PM [74]. There is no detectable change in this localization on receptor stimulation.…”

Section: (B) Localization Of Pitpnm Proteins To Membrane Contact Sitesmentioning

confidence: 84%

“…It has been proposed that the DG may be metabolised via liberation of polyunsaturated fatty acids (PUFA) that may then activate TRP channels [reviewed in [72]]. An interesting feature of RDGA is that in photoreceptors, the protein is localized to the sub-microvillar cisternae (SMC) [73], a specialization of the ER that forms a membrane contact site with the microvillar plasma membrane [reviewed in [74]] This localization of RDGA to an ER sub-compartment resembles, conceptually, the recruitment of DGK and DGK from the ER to the PM of mammalian cells following receptor-mediated PLC activation. In the case of Drosophila photoreceptors, RDGA could act in trans across the small 10 nm gap at this MCS to access DG generated at the microvillar plasma membrane by NORPA.…”

Section: Diacylglycerol Kinasesmentioning

confidence: 99%

Topological organisation of the phosphatidylinositol 4,5-bisphosphate–phospholipase C resynthesis cycle: PITPs bridge the ER–PM gap

Cockcroft

Raghu

2016

Biochemical Journal

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Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) at the plasma membrane (PM) triggering three biochemical consequences, the generation of soluble inositol 1,4,5-trisphosphate (IP), membrane-associated diacylglycerol (DG) and the consumption of PM PI(4,5)P Each of these three signals triggers multiple molecular processes impacting key cellular properties. The activation of PLC also triggers a sequence of biochemical reactions, collectively referred to as the PI(4,5)P cycle that culminates in the resynthesis of this lipid. The biochemical intermediates of this cycle and the enzymes that mediate these reactions are topologically distributed across two membrane compartments, the PM and the endoplasmic reticulum (ER). At the PM, the DG formed during PLC activation is rapidly converted into phosphatidic acid (PA) that needs to be transported to the ER where the machinery for its conversion into PI is localised. Conversely, PI from the ER needs to be rapidly transferred to the PM where it can be phosphorylated by lipid kinases to regenerate PI(4,5)P Thus, two lipid transport steps between membrane compartments through the cytosol are required for the replenishment of PI(4,5)P at the PM. Here, we review the topological constraints in the PI(4,5)P cycle and current understanding how these constraints are overcome during PLC signalling. In particular, we discuss the role of lipid transfer proteins in this process. Recent findings on the biochemical properties of a membrane-associated lipid transfer protein of the PITP family, PITPNM proteins (alternative name RdgBα/Nir proteins) that localise to membrane contact sites are discussed. Studies in both Drosophila and mammalian cells converge to provide a resolution to the conundrum of reciprocal transfer of PA and PI during PLC signalling.

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The Drosophila photoreceptor as a model system for studying signalling at membrane contact sites

Cited by 22 publications

References 32 publications

Phospholipase D activity couples plasma membrane endocytosis with retromer dependent recycling

Phospholipase D activity couples plasma membrane endocytosis with retromer dependent recycling

RDGBα localization and function at membrane contact sites is regulated by FFAT–VAP interactions

Topological organisation of the phosphatidylinositol 4,5-bisphosphate–phospholipase C resynthesis cycle: PITPs bridge the ER–PM gap

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