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Cell Mol Biol Lett
2018 Jul 06;23:32. doi: 10.1186/s11658-018-0093-1.
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Laminopathies: what can humans learn from fruit flies.
Pałka M
,
Tomczak A
,
Grabowska K
,
Machowska M
,
Piekarowicz K
,
Rzepecka D
,
Rzepecki R
.
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Lamin proteins are type V intermediate filament proteins (IFs) located inside the cell nucleus. They are evolutionarily conserved and have similar domain organization and properties to cytoplasmic IFs. Lamins provide a skeletal network for chromatin, the nuclear envelope, nuclear pore complexes and the entire nucleus. They are also responsible for proper connections between the karyoskeleton and structural elements in the cytoplasm: actin and the microtubule and cytoplasmic IF networks. Lamins affect transcription and splicing either directly or indirectly. Translocation of active genes into the close proximity of nuclear lamina is thought to result in their transcriptional silencing. Mutations in genes coding for lamins and interacting proteins in humans result in various genetic disorders, called laminopathies. Human genes coding for A-type lamin (LMNA) are the most frequently mutated. The resulting phenotypes include muscle, cardiac, neuronal, lipodystrophic and metabolic pathologies, early aging phenotypes, and combined complex phenotypes. The Drosophila melanogaster genome codes for lamin B-type (lamin Dm), lamin A-type (lamin C), and for LEM-domain proteins, BAF, LINC-complex proteins and all typical nuclear proteins. The fruit fly system is simpler than the vertebrate one since in flies there is only single lamin B-type and single lamin A-type protein, as opposed to the complex system of B- and A-type lamins in Danio, Xenopus and Mus musculus. This offers a unique opportunity to study laminopathies. Applying genetic tools based on Gal4 and in vitro nuclear assembly system to the fruit fly model may successfully advance knowledge of laminopathies. Here, we review studies of the laminopathies in the fly model system.
Fig. 1. A simplified diagram of the interaction between the protein components of the nuclear lamina and the nuclear envelope with chromatin and the cytoskeleton. Only well documented proteins with high importance for biological functions are demonstrated. Please note that we included two fly-specific proteins (YA and otefin) along with the typical vertebrate proteins. ONM – outer nuclear membrane; INM – inner nuclear membrane; NL – nuclear lamina; NET – nuclear envelope transmembrane proteins; LBR – lamin B receptor; NPC – nuclear pore complex
Fig. 2. a The salivary gland nuclei of 3rd instar larvae with polytene chromosomes are the best known feature of the Drosophila model system. Dissected salivary glands and prepared nuclei are shown, stained for lamin Dm (green) with rabbit affinity purified anti-lamin Dm antibody and lamin C (red) with the ALC28.12 monoclonal antibody. DNA is counterstained with DAPI. b A dissected 3rd instar larvae thick specimen stained for lamin Dm (green) and lamin C (red) with antibodies as in section A. Only differentiated cells express lamin C. Both diploid and polyploid nuclei are visible. c Salivary gland nuclei of 3rd instar larvae, with polytene chromosomes, dissected from a fly strain overexpressing EGFP-lamin Dm (green) under the control of the Act5C-Gal4 driver. Note the increased thickness of the nuclear lamina and its irregular structure, composed of aggregates, cisterns and invaginations. d Nuclei of nurse cells of egg chambers and follicular cells stained for lamin Dm (red) and membranes (green). Drosophila egg chambers contain nurse cells with polyploid nuclei (up to 1024 N) and are frequently used as controls for chromatin organization in polyploid cells without polytene chromosome structure. Please note the diploid oocyte nuclei in which chromatin fills only part of the cell nucleus
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