Alternative Splicing in Class V Myosins Determines Association with Rab10

Roland, Joseph T.; Lapierre, Lynne A.; Goldenring, James R.

doi:10.1074/jbc.m805957200

Cited by 102 publications

(152 citation statements)

References 87 publications

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“…Given that exon D of MYO5 is required for its interaction with Rab10 (ref. 18), we determined MYO5 splicing isoforms in the brain. We found that two isoforms of MYO5B with and without exon D are expressed in the rat brain, whereas MYO5A lacks exon D and MYO5C is not expressed in the brain (Fig.…”

Section: Myo5b Exon D Binds To Gtp-bound Form Of Rab10mentioning

confidence: 99%

“…As shown in Figure 1d, hemagglutinin (HA)-tagged Rab10 was co-precipitated strongly with GFP-tagged MYO5B ( þ D), and weakly with MYO5B ( À D). The weak association between Rab10 and MYO5B ( À D) might be mediated indirectly by common effectors shared by Rab10 and other Rabs, such as Rab11 Family Interacting Protein 2 (FIP2) 18,29 . To determine whether exon D itself is able to bind Rab10, we used beads coupled with glutathione S-transferase (GST)-Rab10 fusion protein to pulldown affinity-purified hexahistidine (His6)-tagged exon D. As shown in Fig.…”

Section: Myo5b Exon D Binds To Gtp-bound Form Of Rab10mentioning

confidence: 99%

“…18). Immunoprecipitation (IP) of cultured rat cortical neurons with anti-MYO5B antibody caused co-IP of Rab10, indicating the association between Rab10 and MYO5B in the brain (Fig.…”

Section: Myo5b Exon D Binds To Gtp-bound Form Of Rab10mentioning

confidence: 99%

“…Among them, the best characterized class is myosin V (MYO5), a family of processive molecular motor with two motor domains connected to extended necks and the globular tails that mediate association with various cargos 13,14 . In mammals, there are three isoforms of MYO5-MYO5A, MYO5B and MYO5C 15 , with each subjecting to alternative splicing in a tissue-specific manner [16][17][18] . A number of studies have shown roles of MYO5 in neuronal transportation, exocytosis and synaptic plasticity 19 .…”

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Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development

Liu

Chen

et al. 2013

Nat Commun

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Polarized membrane addition is crucial for axon development and elongation during neuronal morphogenesis. This process is believed to be regulated by directed membrane trafficking of Rab10-containing post-Golgi carriers. However, the mechanisms underlying the biogenesis of these carriers remain unclear. Here, we report that Rab10 interaction with myosin Vb (MYO5B) determines the formation of Rab10 carriers and is important for axon development. Rab10 interacts with the exon D-encoded domain of MYO5B. Downregulating the expression of MYO5B ( þ D) or blocking its interaction with Rab10 impairs the fission of Rab10 vesicles from trans-Golgi membranes, causes a decrease in the number of Rab10 transport carriers and inhibits axon development in cultured hippocampal neurons. Furthermore, the MYO5B-Rab10 system is required for axon development of vertebrate neocortical neurons or zebrafish retinal ganglion cells in vivo. Thus, specific interaction between Rab10 and MYO5B controls the formation of Rab10 vesicles, which is required for axon development.

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Section: Myo5b Exon D Binds To Gtp-bound Form Of Rab10mentioning

confidence: 99%

Section: Myo5b Exon D Binds To Gtp-bound Form Of Rab10mentioning

confidence: 99%

“…18). Immunoprecipitation (IP) of cultured rat cortical neurons with anti-MYO5B antibody caused co-IP of Rab10, indicating the association between Rab10 and MYO5B in the brain (Fig.…”

Section: Myo5b Exon D Binds To Gtp-bound Form Of Rab10mentioning

confidence: 99%

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confidence: 99%

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Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development

Liu

Chen

et al. 2013

Nat Commun

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“…Three exons within the tail domain (B, D, and F) are expressed in a cell type-specific manner; the predominant melanocyte-and brain-specific isoforms contains exons D, F, and exon B, respectively (13). The exon pattern of myo5a tail likely determines which cargo binds to the motor, because these sequences could serve as binding sites of adaptor proteins: exon D and F are necessary for the binding of Rab10 and melanophilin, respectively (14), (15). In a previous study, we identified the DYNLL2 binding motif of myo5a in a short sequence (Ile1280-Ile1294) situated between the medial and distal coiled-coils of the tail (16).…”

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confidence: 99%

DYNLL2 Dynein Light Chain Binds to an Extended Linear Motif of Myosin 5a Tail That Has Structural Plasticity

Bodor¹,

Radnai²,

Hetényi

et al. 2014

Biochemistry

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LC8 dynein light chains (DYNLL) are conserved homodimeric eukaryotic hub proteins that participate in diverse cellular processes. Among the binding partners of DYNLL2, myosin 5a (myo5a) is a motor protein involved in cargo transport. Here we provide a profound characterization of the DYNLL2 binding motif of myo5a in free and DYNLL2 bound form by using NMR spectroscopy, Xray crystallography and molecular dynamics simulations. In the free form the DYNLL2 binding region, located in an intrinsically disordered domain of the myo5a tail, has a nascent helical character. The motif becomes structured and folds into a β-strand upon binding to DYNLL2. Despite all differences of the myo5a sequence from the consensus binding motif, it accommodates into the same DYNLL2 binding groove as all other partners do. Interestingly, while the core motif shows similar interaction pattern in the binding groove as seen inother complexes, the flanking residues make several additional contacts, thereby lengthening the binding motif. The N-terminal extension folds back and partially blocks the free edge of the β-sheet formed by the binding motif itself. The C-terminal extension contacts the dimer interface and interacts with symmetry related residues of the second myo5a peptide. The involvement of flanking residues of the core binding site of myo5a could modify the quaternary structure of the full-length myo5a and affect its biological functions. The presented structural data widen our understanding of the diverse partner recognition of DYNLL proteins and provide an example of a Janus-faced linear motif. 4The LC8 dynein light chains were originally described as the smallest subunit of the microtubuleassociated cytoplasmic dynein motor complex.They show a highly conserved amino acid sequence throughout evolution and they were later shown to bind to more than 70 other proteins involved in various biological processes, therefore they are now considered hub proteins (1, 2).Vertebrates contain two closely related LC8 paralogs, DYNLL1 and DYNLL2 with partially overlapping functions(1). Under physiological conditions LC8proteins arestable homodimers (3).Atomic resolution structureswere determined both for the apo and ligand-bound form using X-ray crystallographyand NMR spectroscopy (4-6). Five β-strands make up two core β-sheets; one sideof each sheet is flanked by two α-helices, and the otherside forms the dimer interface. The β3-strand of one subunit pairs to theβ2"-strandof the other subunitin an antiparallel mode; and the dimer is stabilized by interface contacts through hydrophobic interactions and side chain H-bonds. Two equivalent grooves are formed and they represent the target binding pockets of the dimer. The primary transcript of the human MYO5A geneis processed by alternative splicing (13). Three exons 5 within the tail domain (B, D, and F) are expressed in a cell type-specific manner; the predominant melanocyte-and brain-specific isoforms contains exons D, F, and exon B, respectively (13). The exon pattern of myo5a tail lik...

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Myosin Vb localises to nucleoli and associates with the RNA polymerase I transcription complex

Lindsay

McCaffrey

2009

Cell Motil. Cytoskeleton

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It is becoming increasingly clear that the mammalian class V myosins are involved in a wide range of cellular processes such as receptor trafficking, mRNA transport, myelination in oligodendrocytes and cell division. Using paralog-specific antibodies, we observed significant nuclear localisation for both myosin Va and myosin Vb. Myosin Vb was present in nucleoli where it co-localises with RNA polymerase I, and newly synthesised ribosomal RNA (rRNA), indicating that it may play a role in transcription. Indeed, its nucleolar pattern was altered upon treatment with RNA polymerase I inhibitors. In contrast, myosin Va is largely excluded from nucleoli and is unaffected by these inhibitors. Myosin Vb was also found to physically associate with RNA polymerase I and actin in co-immunoprecipitation experiments. We propose that myosin Vb serves a role in rRNA transcription.

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Alternative Splicing in Class V Myosins Determines Association with Rab10

Cited by 102 publications

References 87 publications

Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development

Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development

DYNLL2 Dynein Light Chain Binds to an Extended Linear Motif of Myosin 5a Tail That Has Structural Plasticity

Myosin Vb localises to nucleoli and associates with the RNA polymerase I transcription complex

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