jar encodes the sole Drosophila class VI unconventional myosin. Myosin VI is unique among all known myosins because it moves toward the minus (pointed) end of actin filaments, opposite to all other characterized myosins PMID:12134162. This reversal in directionality is due to a unique insert in the converter domain that repositions the lever arm.
From UniProt and InterPro:
- N-terminal SH3-like domain (residues 3-54)
- Myosin motor domain (residues 57-766) with ATP-binding site (residues 151-158)
- Actin-binding region (residues 647-666)
- Class VI-specific lever arm (IPR049016, residues 765-913) -- responsible for minus-end directionality
- IQ domain (residues 808-837) for light chain binding
- Coiled-coil region (residues 900-1022) for dimerization
- Cargo-binding domain (IPR032412, residues 1145-1231)
Four known isoforms from alternative splicing:
- Isoform B (Q01989-1): canonical, expressed throughout life cycle
- Isoform H (Q01989-2): VSP_003343, insert at position 1047
- Isoform I (Q01989-3): VSP_003344/345, altered/truncated C-terminus
- Isoform 145 kDa (Q01989-4): head-specific isoform
The founding functional study showed that jar/95F myosin catalyzes actin-based, ATP-dependent transport of cytoplasmic particles in living Drosophila embryos PMID:8202156. This was the first direct observation of transport by an unconventional myosin in living cells.
Antibody-inhibition studies showed jar is required for proper pseudocleavage furrow formation, nuclear positioning, and actin cap/furrow organization in the syncytial blastoderm PMID:7790355. Disruption leads to aberrant nuclear morphology, actin cytoskeleton disorganization, and spindle defects.
jar is essential for spermatogenesis. It localizes to the leading edge of the individualization complex (IC), which resolves shared membranes into individual spermatid membranes PMID:10588662. Partial loss-of-function mutations cause male sterility. jar stabilizes the branched actin network in actin cones (investment cones) that mediate spermatid separation PMID:16571671. FRAP experiments showed jar remains bound to F-actin for minutes, suggesting a tethering rather than transport role in cones PMID:16571671.
The cargo-binding domain sites are critical for actin structure specialization during individualization PMID:21853045.
jar is involved in intra- and intercellular transport during oogenesis. It is found at ring canals and mediates microfilament-dependent transport of particles (including mitochondria) from nurse cells into the oocyte PMID:9351468.
jar is required for basal targeting of the cell fate determinant Miranda and correct spindle orientation in mitotic neuroblasts PMID:12586070. Miranda directly binds to jar, suggesting active transport of determinants.
jar is required for E-cadherin-mediated border cell migration during oogenesis. It stabilizes E-cadherin and Armadillo (beta-catenin) at the membrane PMID:12134162.
jar plays a role in cell-cell adhesion during dorsal closure. Lethal mutants show detaching cells and irregular epithelial sheets PMID:15454264. Required for egg chamber and imaginal disc morphogenesis PMID:10523504.
jar co-immunoprecipitates with D-CLIP-190 (homolog of CLIP-170), a microtubule-binding protein. They colocalize in neurons and at the posterior pole of embryos PMID:9472041.
RNAi depletion of myosin VI in Drosophila neurons increases retrograde mitochondrial transport, suggesting it opposes (rather than promotes) microtubule-based transport, possibly facilitating organelle docking PMID:20592219.
Proteomics identified multiple cargo-binding partners including Cornetto (microtubule-associated protein). jar and Cornetto are both required for Hedgehog secretion, indicating a role in exocytic trafficking PMID:21368190.
All PMIDs cited in the GOA annotations are REAL and verified:
- PMID:1429838 -- Kellerman & Miller 1992, J Cell Biol -- VERIFIED (initial cloning of 95F MHC)
- PMID:7790355 -- Mermall & Miller 1995, J Cell Biol -- VERIFIED (syncytial blastoderm)
- PMID:8202156 -- Mermall et al 1994, Nature -- VERIFIED (cytoplasmic particle transport)
- PMID:9351468 -- Bohrmann 1997, Cell Mol Life Sci -- VERIFIED (oogenesis transport)
- PMID:9472041 -- Lantz & Miller 1998, J Cell Biol -- VERIFIED (CLIP-190 association)
- PMID:10523504 -- Deng et al 1999, J Cell Sci -- VERIFIED (egg chamber/imaginal disc morphogenesis)
- PMID:10588662 -- Hicks et al 1999, Mol Biol Cell -- VERIFIED (spermatogenesis)
- PMID:12134162 -- Geisbrecht & Montell 2002, Nat Cell Biol -- VERIFIED (border cell migration)
- PMID:12432073 -- Rogat & Miller 2002, J Cell Sci -- VERIFIED (actin dynamics in spermatogenesis)
- PMID:12586070 -- Petritsch et al 2003, Dev Cell -- VERIFIED (neuroblast asymmetric division)
- PMID:12620217 -- Tuxworth & Chia 2003, Mol Cell -- VERIFIED (review/commentary on neuroblast finding)
- PMID:15454264 -- Millo et al 2004, Mech Dev -- VERIFIED (cell-cell adhesion, dorsal closure)
- PMID:16126191 -- Mermall et al 2005, Dev Biol -- VERIFIED (myosin V in spermatid individualization)
- PMID:16571671 -- Noguchi et al 2006, Mol Biol Cell -- VERIFIED (actin stabilization in spermatid individualization)
- PMID:16790438 -- Frank et al 2006, J Biol Chem -- VERIFIED (Androcam as testis light chain)
- PMID:16917818 -- Franke et al 2006, Cell Motil Cytoskeleton -- VERIFIED (nonmuscle myosin II light chain binding)
- PMID:19204120 -- Sousa-Nunes et al 2009, Genes Dev -- VERIFIED (PP4/Miranda localization)
- PMID:20592219 -- Pathak et al 2010, J Neurosci -- VERIFIED (mitochondrial transport)
- PMID:21368190 -- Finan et al 2011, PNAS -- VERIFIED (cargo-binding proteins, Hedgehog secretion)
- PMID:21853045 -- Isaji et al 2011, PLoS One -- VERIFIED (cargo-binding domain in actin cone)
- PMID:25694447 -- Beaven et al 2015, Mol Biol Cell -- VERIFIED (CLIP-190 in nervous system)
PMID:16126191 is primarily about Drosophila myosin V, not myosin VI. The annotation for sperm individualization (GO:0007291) from this paper may be based on the finding that myosin V and myosin VI cooperate during individualization -- the paper studies myosin V mutants and mentions myosin VI context.
PMID:16917818 is about nonmuscle myosin II light chains. Myosin VI (jar) was identified as a binding partner for the essential light chain by mass spectrometry. The myosin VI complex (GO:0031476) and myosin light chain binding (GO:0032027) annotations from this paper are based on co-precipitation data.
The BioReason thinking trace is largely domain-architecture driven. It correctly infers many of the activities from the InterPro domains (motor, lever arm, cargo binding). However: