| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :1.0911733 |
| Thus , melanophilin can associate simultaneously with activated Rab27a and myosin Va via distinct regions , and serve as a linker between these proteins . . 1.0911733^^^ We also show that melanophilin associates with Rab27a and myosin Va on melanosomes in melanocytes , and present evidence that a domain within the carboxyl terminal region of melanophilin interacts with the carboxyl terminal tail of the melanocyte specific splice isoform of myosin Va . 1.0088924^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.63740727 |
| Cosedimentation assays using recombinant proteins reveal that melanophilin directly binds to Rab27a and myosin Va through its N terminal and its first C terminal coiled coil region , respectively . 0.63740727^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.62847231 |
| Although Rab27a binds to myosin Va / melanophilin complex , it did not affect the melanophilin induced activation of myosin Va . 0.62847231^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| We have utilized primary melanocytes to examine the interdependencies between rab27a , myosin Va , and melanophilin . ^^^ The localization of rab27a to melanosomes did not require the function of either myosin Va or melanophilin , but leaden function was required for the association of myosin Va with melanosomes . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Here we show that myosin Va , an actin based vesicle motor , binds to one of its cargoes , the melanosome , by interacting with a receptor protein complex containing Rab27a and melanophilin , a postulated Rab27a effector . ^^^ Rab27a binds to the melanosome first and then recruits melanophilin , which in turn recruits myosin Va . ^^^ Melanophilin creates this link by binding to Rab27a in a GTP dependent fashion through its amino terminus , and to myosin Va through its carboxy terminus . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| However , in contrast to Gln78Leu , Trp73Gly mutant construct neither interacts with the Rab27a effector melanophilin nor modifies melanosome distribution and cytotoxic granule exocytosis . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Slac 2 a ( synaptotagmin like protein ( Slp ) homologue lacking C 2 domains a ) / melanophilin is a melanosome associated protein that links Rab27A on melanosomes with myosin Va , an actin based motor protein , and formation of the tripartite protein complex ( Rab27A . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Rab27a and its rabphilin like effector protein , Melanophilin , recruit myosin Va to melanosomes and appear to serve as the membrane receptor . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Then we studied several key parameters for Rab27a function , including GTP binding and interaction with melanophilin / myosin Va complex , which links melanosomes to the actin network . ^^^ Our results showed that Rab27a L130P can not bind GTP , does not interact with melanophilin , and consequently can not allow melanosome transport on the actin filaments . ^^^ Interestingly , Rab27a W73G binds GTP but does not interact with melanophilin . ^^^ Finally , Rab27a A152P binds both GTP and melanophilin . ^^^ Hence , the interaction of Rab27a with melanophilin / myosin Va is not sufficient to ensure a correct melanosome transport . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Myosin Va isoforms containing exon F are able to colocalize with and influence melanosome distribution by indirect interaction with rab27a and direct interaction with melanophilin . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| The GTPase Rab27A interacts with myosin VIIa and myosin Va via MyRIP or melanophilin and mediates melanosome binding to actin . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Rab 27 acts through organelle specific effector proteins , such as granuphilin in pancreatic beta cells and melanophilin in melanocytes . ^^^ The Rab 27 and effector complex then interacts with proteins that are essential for membrane transport and fusion , such as syntaxin 1a and Munc 18 1 for granuphilin and myosin Va for melanophilin . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Molecules recently identified that participate in this process consist of Rab27a , myosin Va and melanophilin . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| This distribution is due to the interaction with the cortical actin cytoskeleton mediated by a tripartite complex of Rab27a , melanophilin , and myosin Va . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| At the periphery , melanosomes interact with the actin cytoskeleton via a tripartite complex formed by the small GTPase Rab27a , melanophilin and myosin Va , an actin based motor . ^^^ In the retinal pigment epithelium , a similar complex formed by Rab27a , a melanophilin homolog called MyRIP and myosin VIIa is probably responsible for the tethering of melanosomes to the actin cytoskeleton . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Better understood is the case of the melanosome where Rab27a recruits a specific effector called melanophilin , which in turn binds myosin Va . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Our immunofluorescence and yeast two hybrid screening studies reveal that Rab27b can form a tripartite complex on the melanosome membrane with Melanophilin , a Rab27a effector , and protein products of Myosin Va transcripts that contain exon F . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| By contrast , knockdown of Slac 2 a ( also called melanophilin ) , another Rab27A binding protein in melanocytes , caused perinuclear aggregation of melanosomes alone without altering cell shape . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| In mouse melanocytes , myosin Va is recruited onto the surface of melanosomes by a receptor complex containing Rab27a that is present in the melanosome membrane and melanophilin ( Mlp ) , which links myosin Va to Rab27a . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Slac 2 a / melanophilin , the missing link between Rab 27 and myosin Va : implications of a tripartite protein complex for melanosome transport . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| In addition , chimeric analysis of Rab3A and Rab27A showed that the specific sequence of the switch 2 region of Rab 27 isoforms ( especially Leu 84 , Phe 88 , and Asp 91 of Rab27A ) , which is not conserved in the Rab 3 or Rab 8 isoforms , is essential for recognition by the Slac 2 a SHD . ^^^ Synaptotagmin like protein ( Slp ) homology domain 1 of Slac 2 a / melanophilin is a critical determinant of GTP dependent specific binding to Rab27A . ^^^ In this study , systematic deletion analysis and Ala based site directed mutagenesis showed that SHD 1 of Slac 2 a / melanophilin alone is both necessary and sufficient for high affinity specific recognition of the GTP bound form of Rab27A . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Three proteins , Rab27A , myosin Va , and Slac 2 a / melanophilin ( a linker protein between Rab27A and myosin Va ) , are known to be essential for proper actin based melanosome transport in melanocytes . ^^^ Although Slac 2 a directly interacts with Rab27A and myosin Va via its N terminal region ( amino acids 1 to 146 ) and the middle region ( amino acids 241 to 405 ) , respectively , the functional importance of the putative actin binding domain of the Slac 2 a C terminus ( amino acids 401 to 590 ) in melanosome transport has never been elucidated . ^^^ In this study we showed that formation of a tripartite protein complex between Rab27A , Slac 2 a , and myosin Va alone is insufficient for peripheral distribution of melanosomes in melanocytes and that the C terminal actin binding domain of Slac 2 a is also required for proper melanosome transport . ^^^ When a Slac 2 a deletion mutant ( DeltaABD ) or point mutant ( KA ) that lacks actin binding ability was expressed in melanocytes , the Slac 2 a mutants induced melanosome accumulation in the perinuclear region , possibly by a dominant negative effect , the same as the Rab27A binding defective mutant of Slac 2 a or the myosin Va binding defective mutant . ^^^ Our findings indicate that Slac 2 a organizes actin based melanosome transport in cooperation with Rab27A , myosin Va , and actin . . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| In this study we discovered that missense mutations ( I1510N , M1513K and D1519G ) in the globular tail ( GT ) of myosin Va partially impair the binding of Slac 2 a / melanophilin , a linker protein between myosin Va and Rab27A on the melanosome . ^^^ The myosin Va GT binding site in Slac 2 a was mapped to the region ( amino acids 147 240 ) adjacent to the N terminal Rab27A binding site , but it is distinct from the myosin Va exon F binding site ( amino acids 320 406 ) . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Functional analysis of slac 2 a / melanophilin as a linker protein between Rab27A and myosin Va in melanosome transport . ^^^ Slac 2 a / melanophilin regulates melanosome transport in mammalian skin melanocytes by linking melanosome bound Rab27A and an actin based motor protein , myosin Va . ^^^ Mutations in the slac 2 a / mlph gene cause the abnormal pigmentation ( i . e . , perinuclear melanosome aggregation in melanocytes ) in human Griscelli syndrome type 3 and in leaden mice because of the inability to form the tripartite protein complex consisting of Rab27A , Slac 2 a , and myosin Va . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| In vitro Slac 2 c simultaneously directly interacts with both Rab27A and an actin based motor protein , myosin Va , via its N terminal SHD and middle region , respectively , consistent with the fact that the overall structure of Slac 2 c is similar to that of Slac 2 a / melanophilin , a linker protein between Rab27A and myosin Va in the melanosome transport in melanocytes . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Distinct Rab27A binding affinities of Slp 2 a and Slac 2 a / melanophilin : Hierarchy of Rab27A effectors . ^^^ The small GTPase Rab27A has recently been shown to regulate melanosome transport in mammalian skin melanocytes through sequentially interacting with two Rab27A effectors , Slac 2 a / melanophilin and Slp 2 a . ^^^ Although Slac 2 a and Slp 2 a contain a similar N terminal Rab27A binding domain ( named SHD , Slp homology domain ) , nothing is known about the functional differences between the Slac 2 a SHD and Slp 2 a SHD . ^^^ It has been found that they could be classified into a low affinity group ( e . g . , Slac 2 a ) and a high affinity group ( e . g . , Slp 2 a and Slp 4 a ) based on their Rab27A binding affinity . ^^^ Our data suggest that distinct Rab27A binding activities of Slac 2 a and Slp 2 a ensure the order ( or hierarchy ) of Rab27A effectors that sequentially function in melanosome transport in melanocytes . . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Collectively , our data show that Mlph is a critical component of the melanosome transport machinery and suggest that Mlph might function as part of a transport complex with Rab27a and MyoVa . . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| Griscelli syndrome ( GS ) is caused by mutations in the MYO5A ( GS 1 ) , RAB27A ( GS 2 ) , or MLPH ( GS 3 ) genes , all of which lead to a similar pigmentary dilution . ^^^ |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9BV36 and P51159 |
Pubmed |
SVM Score :0.0 |
| NA |
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