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Details on Person UniProt:Q95T12 fwe
| Class:Id | ReferenceGeneProduct:525891 |
|---|---|
| _chainChangeLog | chain:1-194 added on Sat February 7 2015 |
| _displayName | UniProt:Q95T12 fwe |
| _timestamp | 2026-02-20 22:54:34 |
| chain | chain:1-194 |
| checksum | 2D2817158AD73A57 |
| comment | FUNCTION Transmembrane protein which mediates synaptic endocytosis, fitness-based cell culling, neuronal culling, morphogen gradient scaling, and calcium transport (PubMed:20627080, PubMed:23810538, PubMed:25601460, PubMed:28011160, PubMed:33300871, PubMed:35301437). Regulates synaptic endocytosis and hence couples exo- with endocytosis (PubMed:19737521, PubMed:28414717, PubMed:29288152, PubMed:33300871). Controls two major modes of synaptic vesicle (SV) endocytosis in the synaptic boutons of neuromuscular junctions (NMJs); Ca(2+) channel-independent Clathrin-mediated endocytosis (CME) in response to mild stimulation, and Ca(2+) channel-dependent activity-dependent bulk endocytosis (ADBE) in response to strong stimulation (PubMed:28414717, PubMed:33300871). Functions in ADBE and subsequent SV reformation from bulk endosomes by initiating Ca(2+) channel-dependent phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) compartmentalization in synaptic boutons (PubMed:28414717, PubMed:33300871). There it acts at the periactive zone to provide the low Ca(2+) levels required to initiate Calcineurin activation and upregulate PtdIns(4,5)P2 (PubMed:33300871). Conversely PtdIns(4,5)P2 enhances fwe Ca(2+) channel-activity, establishing a positive feedback loop that induces PtdIns(4,5)P2 microdomain at the periactive zone (PubMed:33300871). These microdomains trigger bulk membrane invagination (i.e. ADBE) by triggering actin polymerization while also promoting localization of fwe to bulk endosomes, thereby removing the ADBE trigger to reduce endocytosis and prevent excess membrane uptake (PubMed:33300871). PtdIns(4,5)P2 then promotes SV reformation from the bulk endosomes, to coordinate ADBE and subsequent SV reformation (PubMed:33300871). Different combinations of the flower isoforms at the cell membrane are also required for the identification and elimination of suboptimal or supernumerary cells during development, regeneration, and adulthood (PubMed:20627080, PubMed:20951347, PubMed:23810538, PubMed:25601460, PubMed:28011160, PubMed:30590040). Required for the recognition and elimination of unfit cells in the developing wing during cell competition (PubMed:20627080). Also required for efficient identification and elimination of injured, damaged and/or dysfunctional neurons during regeneration of the adult brain (PubMed:25754635, PubMed:30590040). In the developing pupal retina, mediates the elimination of unwanted postmitotic neurons, including supernumerary photoreceptor neurons that form at the periphery of the retina and are contained within incomplete ommatidia units (PubMed:23810538). Downstream of the flower fitness fingerprints, cells identified as unwanted or unfit are eliminated via apoptosis through the expression of ahuizotl (azot) (PubMed:25601460, PubMed:30590040). However, the cells marked for elimination by the flower isoforms only undergo apoptosis if additional thresholds are met; (1) their neighboring fit/healthy cells express different levels of the fwe isoforms, and (2) the levels of the protective signal SPARC expressed by the loser or unwanted cells are unable to inhibit caspase activation (PubMed:20627080, PubMed:20951347, PubMed:23810538). These additional thresholds for flower-mediated apoptosis, allows useful cells to recover from transient and limited stress before they are unnecessarily eliminated (PubMed:20951347). Functions with dally and magu in a mechanism of scaling, which utilises apoptosis to ensure that the dpp morphogen gradient, which mediates organ growth, remains proportional to the size of the growing wing (PubMed:35301437). In this mechanism, fwe represses dally- and Magu-dependent activity in expanding the gradient, and dally/Magu inhibits fwe-dependent apoptosis to keep cell death rate low (PubMed:35301437). When the levels of these different proteins are optimally regulated the gradient correctly scales with organ growth but when this fails, fwe-mediated apoptosis is activated to trim the developing tissue to match the correct size of the gradient (PubMed:35301437).FUNCTION Functions with the other flower isoforms to produce tissue-specific fitness fingerprints that identify unfit or fit cells during cell selection processes in order to maintain tissue health (PubMed:20627080, PubMed:25601460). In the wing imaginal disk, this isoform is highly expressed in healthy/normal cells but is down-regulated in cells with decreased fitness (PubMed:20627080). During cell competition, if levels of this isoform in unfit cells is lower than in the surrounding neighboring cells, the suboptimal cells are recognized as 'loser' cells, and undergo elimination via apoptosis to be replaced by the surrounding healthy 'winner' cell population (PubMed:20627080).FUNCTION Functions with the other flower isoforms to produce tissue-specific fitness fingerprints that identify unfit or fit cells during cell selection processes in order to maintain tissue health (PubMed:20627080, PubMed:25601460). In the wing imaginal disk, this isoform displays low levels of expression in healthy/normal cells but is up-regulated in cells with decreased fitness (PubMed:20627080, PubMed:25601460). During cell competition, if levels of this isoform in unfit cells is higher than in the surrounding neighboring cells, the suboptimal cells are recognized as 'loser' cells, and undergo elimination via apoptosis to be replaced by the surrounding healthy 'winner' cell population (PubMed:20627080, PubMed:25601460).FUNCTION Functions with the other flower isoforms to produce tissue-specific fitness fingerprints that identify unfit cells for cell selection processes during development, regeneration, and to maintain tissue health (PubMed:20627080, PubMed:25601460, PubMed:25754635, PubMed:30590040). During cell competition in certain tissues, marks suboptimal or damaged cells as 'loser' cells (PubMed:20627080, PubMed:25601460, PubMed:25754635, PubMed:30590040). In cells of the wing imaginal disk and damaged or dysfunctional neurons in the adult optic lobe, this isoform displays low to no expression in healthy/normal cells but is up-regulated in cells with decreased fitness or damage-affected neurons (PubMed:20627080, PubMed:25754635, PubMed:30590040). During cell competition, if levels of this isoform in unfit cells is higher than in the surrounding neighboring cells, the suboptimal cells are recognized as 'loser' cells, and undergo elimination via apoptosis to be replaced by the surrounding healthy/undamaged 'winner' cell population (PubMed:20627080, PubMed:25754635, PubMed:30590040). In the developing pupal retina, also required for the recognition and elimination of postmitotic neurons, including supernumerary photoreceptor neurons that form at the periphery of the retina and are contained within incomplete ommatidia units (PubMed:23810538). Activity at the peripheral retina is induced by the wg signaling pathway but, once activated, it promotes apoptosis of supernumerary photoreceptor neurons independently of wg signaling and snail function (PubMed:23810538).ACTIVITY REGULATION Channel activity is inhibited by La(3+), which reduces Ca(2+) influx and thus inhibits its function in promoting activity-dependent bulk endocytosis (ADBE) in response to high stimuli.SUBUNIT Associates with the dally/ magu complex.SUBUNIT Homomultimer (PubMed:19737521). Associates with the dally/ magu complex (PubMed:35301437).SUBUNIT Associates with the dally/ magu complex.INTERACTION Upon fusion of the synaptic vesicle (SV) with the presynaptic membrane, protein transfers from the SV to the periactive zones where endocytosis is known to occur (PubMed:19737521, PubMed:28414717, PubMed:33300871). Upon high K(+) stimulation, expression levels in NMJ boutons are higher in bulk endosomes than in synaptic vesicles, suggesting that it is recycled to bulk endosomes after it activates ADBE (PubMed:33300871).SUBCELLULAR LOCATION Localizes to the apico-lateral membranes in wing imaginal disks and salivary gland cells.SUBCELLULAR LOCATION Detected in the imaginal wing disk (at protein level).TISSUE SPECIFICITY Detected throughout the adult brain, including the optic lobe but, at much lower levels of expression than isoform Lose-A.TISSUE SPECIFICITY Detected in the optic lobe (at protein level) (PubMed:25754635). Detected throughout the adult brain, including the optic lobe (PubMed:25754635, PubMed:30590040). Expressed in damaged and undamaged optic lobe neurons (PubMed:25754635, PubMed:30590040).TISSUE SPECIFICITY Expressed in optic lobe neurons, with higher levels of expression in suboptimal neurons (PubMed:30590040). Specifically expressed in injury-damaged optic lobe neurons (PubMed:25754635).DEVELOPMENTAL STAGE Detected in all imaginal disk cells and salivary gland cells (at protein level) (PubMed:20627080). In pupae, ubiquitously expressed in the retina including the neuronal layer (at protein level) (PubMed:23810538).DEVELOPMENTAL STAGE In pupal retinas, detected at 24 hr after pupal formation (APF) to 42 hr APF, where it is ubiquitously expressed throughout the retina including the neuronal layer (at protein level) (PubMed:23810538). Expressed in the neuropils of embryonic, larval, adult CNS, and R1-R6 terminals. Expression in the central nervous system (CNS) starts at embryonic stage 13 (PubMed:19737521).DEVELOPMENTAL STAGE In pupal retinas, specifically expressed at the periphery in photoreceptor neurons that are undergoing apoptosis (at protein level) (PubMed:23810538). Expression in the pupal retinas is not detected until 36 hr after pupal formation (APF) and is maintained until 44 hr APF; this is during the retina 'late cell death' event when peripheral ommatidia are being eliminated from the final structure (at protein level) (PubMed:23810538).INDUCTION Induced in the midgut and adult brain by tissue damage caused by UV irradiation.INDUCTION Induced in the midgut and adult brain by tissue damage caused by UV irradiation (PubMed:25601460). Up-regulated in optic lobe neurons that have been damaged by lesioning the optic lobe unilaterally causing penetrating traumatic brain injury (PubMed:25754635).DISRUPTION PHENOTYPE Lethal; mutants die either during the embryonic stage or the first instar larval stage (PubMed:28011160). Embryos frequently display head involution defects, some do not develop a cuticle and/or occasionally display dorsal closure defects (PubMed:28011160). The nervous system of embryos also displays developmental defects (PubMed:19737521, PubMed:20627080). In presynaptic terminals, intracellular resting calcium levels and endocytosis is impaired, whereas exocytosis is normal (PubMed:19737521). Boutons at the neuromuscular junctions exhibit a significant depletion in the number of synaptic vesicles (PubMed:19737521). There are numerous extra boutons which are often small, clustered, and flowery in nature (PubMed:19737521). Mutant nerve terminals display omega structures and collared pits (PubMed:19737521). RNAi-mediated knockdown in wing disks reduces cell apoptosis during Myc-mediated cell competition experiments (PubMed:28011160, PubMed:35301437). RNAi-mediated knockdown in the posterior compartment of the wing disk, has no effect on tissue growth under normal conditions however, growth is reduced in tissues undergoing Myc-mediated cell competition (PubMed:20627080). RNAi-mediated knockdown during Myc-mediated cell competition experiments, has no effect on up-regulation of SPARC in loser cells (PubMed:20951347).DISRUPTION PHENOTYPE RNAi-mediated knockdown in the posterior compartment of the wing disk, does not induce apoptosis and has no effect on compartment growth.MISCELLANEOUS The name 'flower' derives from mutants that display numerous extra boutons that are small, clustered, and flowery in nature.SIMILARITY Belongs to the calcium channel flower family. |
| created | [InstanceEdit:525883] Kanapin, AA |
| description | recommendedName: fullName evidence="16"Calcium channel flower shortName evidence="16"3L5 |
| geneName | fwe flower CG6151 |
| identifier | Q95T12 |
| isSequenceChanged | FALSE |
| keyword | Alternative splicing Calcium Calcium channel Calcium transport Cell membrane Cell projection Cytoplasmic vesicle Endocytosis Endosome Ion channel Ion transport Membrane Reference proteome Synapse Transmembrane Transmembrane helix Transport |
| modified | [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9796772] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | fwe |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | FLOWR_DROME Q8IQM8 Q9VUU2 |
| sequenceLength | 194 |
| species | [Species:56210] Drosophila melanogaster |
| (isoformParent) | [ReferenceIsoform:525892] UniProt:Q95T12-1 fwe [Drosophila melanogaster] [ReferenceIsoform:525893] UniProt:Q95T12-2 fwe [Drosophila melanogaster] [ReferenceIsoform:525894] UniProt:Q95T12-3 fwe [Drosophila melanogaster] |
| (referenceEntity) | [EntityWithAccessionedSequence:5263621] fwe [plasma membrane] [Drosophila melanogaster] |
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No pathways have been reviewed or authored by UniProt:Q95T12 fwe (525891)
