lgl, lethal giant larvae, p127, dlgl, p127l(2)gl
Gene model reviewed during 5.44
Annotated transcripts do not represent all supported alternative splices within 5' UTR.
Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.45
Multiphase exon postulated: exon reading frame differs in alternative transcripts.
May form multimeric complexes. Interacts with mahj. Interacts with aPKC; the interaction results in phosphorylation of l(2)gl.
Phosphorylated by aPKC which restricts l(2)gl activity to the oocyte posterior and is required for oocyte polarity formation.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\l(2)gl using the Feature Mapper tool.
The l(2)gl protein is localized at cellular membranes or the intercellular matrix.
The l(2)gl protein is found in all primordia of larval tissues in the embryo. Neural primordia are only weakly labelled with the exception of the presumptive optic centers and axon bundles of the ventral cord which are distinctly labelled. In larvae, l(2)gl protein is seen at low levels until the end of the third instar where it is found mainly in brain and imaginal discs.
GBrowse - Visual display of RNA-Seq signalsView Dmel\l(2)gl in GBrowse 2
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for identity of: l(2)gl CG2671
A high incidence of mutant alleles found in natural populations in the Soviet Union (Golubovsky and Sokolova, 1973). Most tested alleles are molecular deficiencies with one breakpoint distal to the origin of the 40 kb walk and the other as indicated in allele list. Only l(2)gl52, which has a 10 kb insertion, and l(2)gl275, in which 7.9 kb have been deleted and replaced by an insert of 6.5 kb, are exceptions.
Second chromosome stocks often contain second-site deletions uncovering l(2)gl, the high frequency probably being due to the fact that l(2)gl is the second protein coding gene downstream of the subtelomeric region of chromosome 2L.
Overexpression of l(2)gl in D.melanogaster males results in paternal-effect lethality that mimics the fertilisation defects associated with cytoplasmic incompatibility (CI) caused by Wolbachia infection.
dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.
dsRNA made from templates generated with primers directed against this gene is tested in an RNAi screen for effects on actin-based lamella formation.
l(2)gl protein is uniformly cortical and interact with several types of myosin to localise neuroblast fate determinants.
The l(2)gl and dlg1 gene products regulate basal protein targeting, but not apical complex formation or spindle orientation, in both embryonic and larval neuroblasts. The l(2)gl and dlg1 proteins promote, and that of zip inhibits, actomyosin dependent basal protein targeting in neuroblasts.
l(2)gl plays a critical role at the onset of vitellogenesis and regulates growth of the oocyte, follicle cell migration and organisation and germline cell viability.
Genetic analysis of l(2)gl reveal function is required during embryonic and post-embryonic development to maintain the normal developmental capacity.
Some of the proteins of apico-lateral junctions are required both for apico-basal cell polarity and for the signalling mechanisms controlling cell proliferation, whereas others are required more specifically in cell-cell signalling.
l(2)gl function is required for proper development during early embryogenesis.
p127 protein of l(2)gl is able to build quaternary structures forming a network with which other proteins associate. As revealed by the tumorous phenotype, organisation of the p127 network and its association with other proteins plays critical roles in the control of cell proliferation.
The l(2)gl product is required in vivo in different types of epithelial cells to control their shape during development.
The p127 protein of the l(2)gl gene is a component of a cytoskeletal network when complexed with a nonmuscle myosin II heavy chain protein, zip. Partial disruption of this complex causes l(2)gl gene inactivation and neoplastic transformation.
l(2)gl p127 protein is a component of a cytoskeletal network extending in the cytoplasm and/or underlaying the inner face of the plasma membrane in a variety of cells and tissues.
Mutants display a brain and imaginal disc neoplastic phenotype.
Mutations in l(2)gl cause malignant tumours in the brain and imaginal discs and generate developmental defects in a number of other tissues. Cellular and subcellular localisation of the protein to the cytoplasm and the inner face of the lateral cell membrane suggests that changes in cell shape and the loss of apical-basal polarity observed in tumorous tissues are a direct result of alterations in the cytoskeleton organisation caused by l(2)gl inactivation. Results also suggest the protein is involved in a cytoskeletal-based intercellular communication system directing cell differentiation.
The structure of the cytosolic form of l(2)gl protein confirms that the protein is a component of the cytoskeletal network including myosin and suggests that the neoplastic transformation resulting from l(2)gl gene inactivation may be caused by the partial disruption of this network.
When l(2)gl mutant brains are transplanted into wild-type adult hosts they can develop into enormous tumors. Using antibodies against the human 72kD type IV collagenase (differentially expressed in metastatic tumors), a cross reacting gelatinase of 49kD has been identified which is increased in l(2)gl mutant vs wild-type brains. Tumor cells that invade host tissues express Gelatinase, suggesting that the metastasis of Drosophila cells is similar to the metastasis of some human tumors at the biochemical as well as the cellular level.
awd function is required for brain tumour formation or proliferation in l(2)gl mutants. Mutant l(2)gl induced neuroblastomas are invasive and mutants have an increased proportion of awd expressing cells in the brain.
The highly divergent cis-regulatory elements of Dpse\l(2)gl can be fully recognized in D.melanogaster and lead to the synthesis of a transgenic protein that has enough specificity conserved for replacing the tumor-suppressor function normally fulfilled by the D.melanogaster l(2)gl protein.
Neoplastic growth takes place in clones of cells that have lost l(2)gl in the preblastoderm syncytial embryos prior to any l(2)gl expression. Clones produced at the embryonic stages do not display the neoplastic phenotype and clones that arise in the larval stages show near normal or normal development. This analysis demonstrates the critical period for the establishment of tumorigenesis occurs during early embryogenesis at a time when l(2)gl expression is most intense in all cells. P-element transformation of l(2)gl deletion derivatives identify the essential domains.
The transcription patterns of Abl, R, Ras85D and Src64B were analyzed in neuroblasts derived from tumerous larval brain of l(2)gl larvae and S2 tissue culture cells.
Monoclonal antibodies have been raised against the l(2)gl protein and distribution patterns demonstrate that the l(2)gl protein is involved in proliferation arrest of cells.
The phenotype of a number of homozygous and transheterozygous l(2)gl mutants has been studied.
The viability of 7 l(2)gl alleles in heterozygotes has been studied at different temperatures. At 25oC, viability of the heterozygotes is reduced, but at low (12, 17oC) and high (29-30oC) temperatures the heterozygotes have a considerable advantage compared to wild-type.
Homozygotes undergo embryogenesis and the first three larval instars; larvae reach normal maximum size; then for some alleles most homozygotes fail to pupate, becoming bloated and 1.5-2 times normal size, whereas for others the majority form prepupae but fail to progress into morphogenesis. Ring gland small and appears immature in third instar larvae (Scharrer and Hadorn, 1938); third instar l(2)gl larvae implanted with a normal ring gland pupate but do not metamorphose; injection of ecdysone elicits the same result (Karlson and Hanser, 1952); thus a deficiency of hormones from the ring gland is probably one, but not the only, result of l(2)gl. Homozygotes that die as prepupae have underdeveloped corpora allata and prothoracic glands, whereas larval lethals have underdeveloped prothoracic glands but normal corpora allata (Korochkina and Nazarova, 1977). Prothoracic glands contain approximately 1% the normal quantity of smooth endoplasmic reticulum (Aggarwal and King, 1969). Alleles range from 98% larval and 2% pupal death to 18% larval and 82% pupal death (Gateff, Golubovsky and Sokolova, 1977). In the most extreme phenotypes, the larval brain and optic lobes become enlarged and disorganized and the imaginal discs large and clumped; when discs of such larvae are transplanted into wild-type-female abdomens, they form large contained tumors, whereas transplanted optic primordia from larval brains form invasive neuroblastomas, which grow rapidly, killing the host within 7-14 days; they can be serially cultured in adult abdomens (Gateff and Schneiderman, 1974). These observations have led to l(2)gl's being designated a Drosophila oncogene. Intermediate alleles exhibit moderately enlarged brain and discs, which show enhanced growth when transplanted into wild-type females and death of host is delayed. In weak alleles the brain and discs are small and rudimentary and grow slowly in transplants. One allele (l(2)gl558) normal in disc morphology and behavior in transplants. The lethal phase is not well correlated with the phenotypic expression. Most abundant transcription noted in early (0-6 h) embryos and late third instar larvae, with the smaller transcript more abundant in embryos and the larger in larvae (Mechler, McGinnis and Gehring, 1985). Immunocytochemistry shows localization of l(2)gl product at cell surfaces, specifically at the interfaces between proliferating cells (Klambt and Schmidt, 1986; Klambt, Muller, Lutzelschwab, Rossa, Totzke and Schmid; Lutzelschwab, Klambt, Rossa and Schmidt, 1987). During later embryogenesis relatively high amounts of l(2)gl protein is detected in pole cells and cells of the developing nervous system; specifically neurons in the peripheral nervous system undergoing axogenesis express the protein. Monoclonal antibodies specifically stain junctions between mammalian cells in culture as though they are recognizing either membrane or intercellular-matrix proteins (Klambt et al., 1989). Ten-to-eleven-day-old larvae homozygous for larval-lethal alleles exhibit remarkably few puff sites, only 63BC and occasionally 88D and 89B; however, heat shock induced puffs develop normally (Ashburner, 1970). Homozygotes able to form prepupae exhibit more nearly normal puffing patterns; puffing in response to administration of ecdysone also appears normal (Richards, 1976).