The following text describes a protein:
Function:
Transmembrane protein which mediates synaptic endocytosis, fitness-based cell culling, neuronal culling, morphogen gradient scaling, and calcium transport. Regulates synaptic endocytosis and hence couples exo- with endocytosis. 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. 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. 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. 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. 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. PtdIns(4,5)P2 then promotes SV reformation from the bulk endosomes, to coordinate ADBE and subsequent SV reformation. 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. Required for the recognition and elimination of unfit cells in the developing wing during cell competition. 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. Also required for efficient elimination and replacement of old neurons by newly generated neurons during regeneration in the adult brain following mechanical injury. Downstream of the flower fitness fingerprints, cells identified as unwanted or unfit are eliminated via apoptosis through the expression of ahuizotl (azot). 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. These additional thresholds for flower-mediated apoptosis, allows useful cells to recover from transient and limited stress before they are unnecessarily eliminated. 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. 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. 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.
Subcellular Localization:
Cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Multi-pass membrane protein. Presynaptic cell membrane. Endosome. Note=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. 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.
Sequence:
MSFAEKITGLLARPNQQDPIGPEQPWYLKYGSRLLGIVAAFFAILFGLWNVFSILTLNVSCLVAGIIQMVAGFVVMLLEAPCCFVCFEQVNVIADKVDSKPLYFRAGLYIAMAIPPIILCFGLASLFGSGLILGTGVVYGMMALGKKASADDMRAAAQQTFGGNTPAQTNDRAGIVNNAQPFSFTGAVGTDSNV