Slac2-a/Melanophilin, the Missing Link between Rab27 and Myosin Va

Myosin Va is a member of the unconventional class V myosin family, and a mutation in themyosin Va gene causes pigment granule transport defects in human Griscelli syndrome and dilute mice. How myosin Va recognizes its cargo (i.e. melanosomes), however, has re- mained undetermined over the past decade. In this study, we discovered Slac2-a/melanophilin to be the “missing link” between myosin Va and GTP-Rab27A present in the melanosome. Deletion analysis and site-directed mutagenesis showed that the N-terminal Slp (synaptotagmin-like protein) homology domain of Slac2-a specifically binds Rab27A/B isoforms and that the C-terminal half directly binds the globular tail of myosin Va. The tripartite protein complex (Rab27A· Slac2-a·myosin Va) in melanoma cells was further confirmed by immunoprecipitation. The discovery that myosin Va indirectly recognizes its cargo through Slac2-a, a novel Rab27A/B effector, should shed light on molecular recognition of its specific cargo by class V myosin.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-04-05

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.C200005200PMID 11856727
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Slp Homology Domain of Synaptotagmin-like Proteins 1–4 and Slac2 Functions as a Novel Rab27A Binding Domain*

  2002cited by this paper
• Synaptotagmin IX Regulates Ca2+-dependent Secretion in PC12 Cells*

  2002cited by this paper
• Rab27a Is Required for Regulated Secretion in Cytotoxic T Lymphocytes

  2001cited by this paper
• JFC1, a Novel Tandem C2 Domain-containing Protein Associated with the Leukocyte NADPH Oxidase*

  2001cited by this paper
• Rab proteins as membrane organizers

  2001cited by this paper
• The melanosome: membrane dynamics in black and white

  2001cited by this paper
• Myosin vb is associated with plasma membrane recycling systems.

  2001cited by this paper
• Rab27a: A key to melanosome transport in human melanocytes.

  2001cited by this paper
• Defective Granule Exocytosis in Rab27a-Deficient Lymphocytes from Ashen Mice

  2001cited by this paper
• The N-terminal cysteine cluster is essential for membrane targeting of B/K protein

  2001cited by this paper
• Rab27a Regulates the Peripheral Distribution of Melanosomes in Melanocytes

  2001cited by this paper
• The C2A domain of double C2 protein gamma contains a functional nuclear localization signal.

  2001cited by this paper
• Novel splicing isoforms of synaptotagmin-like proteins 2 and 3: identification of the Slp homology domain.

  2001cited by this paper
• The C2A Domain of Double C2 Protein γ Contains a Functional Nuclear Localization Signal*

  2001cited by this paper
• A Switch to Release the Motor

  2001cited by this paper
• Rab27a enables myosin Va-dependent melanosome capture by recruiting the myosin to the organelle.

  2001cited by this paper
• Mechanism of the SDS-resistant Synaptotagmin Clustering Mediated by the Cysteine Cluster at the Interface between the Transmembrane and Spacer Domains*

  2001cited by this paper
• Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice

  2001cited by this paper
• Cell biology. A switch to release the motor.

  2001cited by this paper
• Synaptotagmin-like protein 1-3: a novel family of C-terminal-type tandem C2 proteins.

  2001cited by this paper
• Tac2‐N, an atypical C‐type tandem C2 protein localized in the nucleus 1

  2001cited by this paper
• Mechanism of the Calcium-dependent Multimerization of Synaptotagmin VII Mediated by Its First and Second C2 Domains*

  2001cited by this paper
• The N-terminal cysteine cluster is essential for membrane targeting of B/K protein.

  2001cited by this paper
• Synaptotagmins in membrane traffic: which vesicles do the tagmins tag?

  2000cited by this paper
• Local calcium release in dendritic spines required for long-term synaptic depression.

  2000cited by this paper
• Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome

  2000cited by this paper
• Myosins: a diverse superfamily.

  2000cited by this paper
• Distinct self-oligomerization activities of synaptotagmin family. Unique calcium-dependent oligomerization properties of synaptotagmin VII.

  2000cited by this paper
• A mutation in Rab27a causes the vesicle transport defects observed in ashen mice.

  2000cited by this paper
• Class V myosins.

  2000cited by this paper
• Double C2 protein. A review.

  2000cited by this paper
• A Novel Alternatively Spliced Variant of Synaptotagmin VI Lacking a Transmembrane Domain

  1999cited by this paper
• A novel alternatively spliced variant of synaptotagmin VI lacking a transmembrane domain. Implications for distinct functions of the two isoforms.

  1999cited by this paper
• Novel Rabphilin-3-like Protein Associates with Insulin-containing Granules in Pancreatic Beta Cells*

  1999cited by this paper
• Conserved N-terminal Cysteine Motif Is Essential for Homo- and Heterodimer Formation of Synaptotagmins III, V, VI, and X*

  1999cited by this paper
• Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A.

  1999cited by this paper
• Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

  1998cited by this paper
• Brain Myosin V Is a Synaptic Vesicle-associated Motor Protein: Evidence for a Ca2+-dependent Interaction with the Synaptobrevin–Synaptophysin Complex

  1997cited by this paper
• Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

  1997cited by this paper
• The C2 domain calcium‐binding motif: Structural and functional diversity

  1996cited by this paper
• The dilute-lethal (dl) gene attacks a Ca2+ store in the dendritic spine of Purkinje cells in mice.

  1996cited by this paper
• Functional Diversity of C2 Domains of Synaptotagmin Family

  1995cited by this paper
• Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II.

  1994cited by this paper
• Novel myosin heavy chain encoded by murine dilute coat colour locus

  1991cited by this paper
• pEF-BOS, a powerful mammalian expression vector.

  1990cited by this paper
• Dilute suppressor dsu acts semidominantly to suppress the coat color phenotype of a deletion mutation, dl20J, of the murine dilute locus.

  1988cited by this paper
• Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.

  1988cited by this paper

• Insights into lysosome-related organelle biogenesis: melanosome as a model organelle

  2026cites this paper
• AID–2×RBD27, an auxin-inducible degron-based Rab27 trapper that reversibly inhibits the function of Rab27A in melanocytes

  2025cites this paper
• Transcriptional regulation of Mlph and Rab27a by PAX3-NF-κB interaction in melanosome transport of melanocytes.

  2025cites this paper
• Comparison of Transcriptome Differences in Scales of Two Closely Related Snake Species (Lycodon rufozonatus and Lycodon rosozonatus)

  2025cites this paper
• A novel, rapidly progressive ataxia due to a spontaneous Myo5a mutation in mice impairs transport proteins and alters mitochondria

  2025cites this paper
• A review on evolution, structural characteristics, interactions, and regulation of the membrane transport protein: The family of Rab proteins.

  2025cites this paper
• The Melanophilin knockout chicken, as a new alopecia animal model

  2025cites this paper
• Identification of a third myosin-5a-melanophilin interaction that mediates the association of myosin-5a with melanosomes

  2024cites this paper
• Trefoil Factor 2 Expressed by the Murine Pancreatic Acinar Cells Is Required for the Development of Islets and for β-Cell Function During Aging

  2024cites this paper
• Impact of Rab27 on Melanoma Cell Invasion and sEV Secretion

  2024cites this paper
• Memory induced-mechanism of noise attenuator of myosin V molecular motors

  2024cites this paper
• Up-regulation of Melanophilin (MLPH) gene during avian adipogenesis and decreased fat pad weights with adipocyte hypotrophy in MLPH knockout quail

  2024cites this paper
• Melanophilin regulates dendritogenesis in melanocytes for feather pigmentation

  2024cites this paper
• Molecular basis of platelet granule defects.

  2024cites this paper
• Whitening effects of fermented Trigonotis radicans var. sericea with Lactobacillus brevis in α-MSH-stimulated B16F10 melanoma cells

  2024cites this paper
• MLPH is a novel adipogenic factor controlling redox homeostasis to inhibit lipid peroxidation in adipocytes.

  2024cites this paper
• The role of SPIRE actin nucleators in cellular transport processes.

  2023cites this paper
• Mitochondria–Melanocyte cellular interactions: An emerging mechanism of vitiligo pathogenesis

  2023cites this paper
• A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy

  2023cites this paper
• A Comprehensive Review of Mammalian Pigmentation: Paving the Way for Innovative Hair Colour-Changing Cosmetics

  2023cites this paper
• Genomic Landscape of Copy Number Variations and Their Associations with Climatic Variables in the World’s Sheep

  2023influential citation
• Bitesize bundles F-actin and influences actin remodeling in syncytial Drosophila embryo development

  2023influential citation
• Inhibition of Melanosome Transport by Inducing Exon Skipping in Melanophilin

  2023cites this paper
• Differential Myosin 5a splice variants in innervation of pelvic organs

  2023cites this paper
• Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism (FBP1, ACAD9) and vesicle trafficking (RAB27A)

  2023cites this paper
• A frameshift variant in the melanophilin gene is associated with loss of pigment from shed skin in ball pythons ( Python regius )

  2023cites this paper
• KIF13A—A Key Regulator of Recycling Endosome Dynamics

  2022cites this paper
• Biosynthesis, intracellular-trafficking, and exocytosis of insulin granules

  2022cites this paper
• Myosin 5a in the Urinary Bladder: Localization, Splice Variant Expression, and Functional Role in Neurotransmission

  2022cites this paper
• Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient

  2022cites this paper
• Early-stage structure-based drug discovery for small GTPases by NMR spectroscopy.

  2022cites this paper
• 5G Electromagnetic Radiation Attenuates Skin Melanogenesis In Vitro by Suppressing ROS Generation

  2022cites this paper
• Griscelli Syndrome Type 3 in Siblings

  2022cites this paper
• Manipulation of PD‐L1 Endosomal Trafficking Promotes Anticancer Immunity

  2022cites this paper
• Rab32/38-Dependent and -Independent Transport of Tyrosinase to Melanosomes in B16-F1 Melanoma Cells

  2022cites this paper
• Large Rab GTPase Rab44 regulates microtubule-dependent retrograde melanosome transport in melanocytes

  2022cites this paper
• Epimedium brevicornum Maxim. Extract exhibits pigmentation by melanin biosynthesis and melanosome biogenesis/transfer

  2022cites this paper
• Suppression of PD‐L1 release from small extracellular vesicles promotes systemic anti‐tumor immunity by targeting ORAI1 calcium channels

  2022cites this paper
• Diagnostic and therapeutic caveats in Griscelli syndrome

  2021cites this paper
• Decoding the Evolution of Melanin in Vertebrates.

  2021cites this paper
• Regulation of Melanophilin (Mlph) gene expression by the glucocorticoid receptor (GR)

  2021cites this paper
• Expression of Myosin 5a splice variants in murine stomach

  2021cites this paper
• Integrated analysis of mRNA-seq and microRNA-seq depicts the potential roles of miRNA-mRNA networks in pigmentation of Chinese soft-shelled turtle (Pelodiscus sinensis)

  2021cites this paper
• In vivo Roles of Rab27 and Its Effectors in Exocytosis

  2021cites this paper
• Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement

  2020cites this paper
• A novel function of Prohibitin on melanosome transport in melanocytes

  2020cites this paper
• Association of Melanophilin (MLPH) gene polymorphism with coat colour in Rex rabbits

  2020cites this paper
• LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade

  2020cites this paper
• Analysis of Genome DNA Methylation at Inherited Coat Color Dilutions of Rex Rabbits

  2020cites this paper
• Molecular regulation of the plasma membrane-proximal cellular steps involved in NK cell cytolytic function

  2020cites this paper
• Rab GTPases: Key players in melanosome biogenesis, transport, and transfer

  2020cites this paper
• RAB27A/Melanophilin blocker inhibits melanoma cell motility and invasion.

  2020cites this paper
• The Expression, Clinicopathologic Characteristics, and Prognostic Value of Androgen Receptor in Breast Cancer: A Bioinformatics Analysis Using Public Databases

  2020cites this paper
• Melanophilin Accelerates Insulin Granule Fusion without Predocking to the Plasma Membrane

  2020cites this paper
• In Vitro Fluorescence Resonance Energy Transfer-Based Assay Used to Determine the Rab27-Effector-Binding Affinity

  2020cites this paper
• A Stop-Gain Mutation within MLPH Is Responsible for the Lilac Dilution Observed in Jacob Sheep

  2020cites this paper
• The Urothelium: Life in a Liquid Environment.

  2020cites this paper
• A comprehensive analysis of Rab GTPases reveals a role for Rab34 in serum starvation-induced primary ciliogenesis

  2020cites this paper
• Rab27 GTPases regulate alpha-synuclein uptake, cell-to-cell transmission, and toxicity

  2020cites this paper
• Calcium triggers the dissociation of myosin‐Va from ribosomes in ribonucleoprotein complexes

  2020cites this paper
• Therapeutic targeting of neutrophil exocytosis

  2020cites this paper
• The physiology of melanin deposition in health and disease.

  2019cites this paper
• The role and mechanism of Asian medicinal plants in treating skin pigmentary disorders.

  2019cites this paper
• The adaptor protein melanophilin regulates dynamic myosin-Va:cargo interaction and dendrite development in melanocytes

  2019cites this paper
• Rab10 regulates tubular endosome formation through KIF13A and KIF13B motors

  2019cites this paper
• Motor-cargo adaptors at the organelle-cytoskeleton interface.

  2019cites this paper
• Comprehensive knockout analysis of the Rab family GTPases in epithelial cells

  2019cites this paper
• Exploring the iceberg: Prospects of coordinated myosin V and actin assembly functions in transport processes

  2019cites this paper
• Myosin Va and spermine synthase: partners in exosome transport

  2019cites this paper
• Unveiling the interaction between the molecular motor Myosin Vc and the small GTPase Rab3A.

  2019cites this paper
• Unconventional Myosins: How Regulation Meets Function

  2019cites this paper
• Involvement of ARHGEF10, GEF for RhoA, in Rab6/Rab8-mediating membrane traffic

  2019cites this paper
• RAB27A promotes melanoma cell invasion and metastasis via regulation of pro‐invasive exosomes

  2019cites this paper
• The road to lysosome‐related organelles: Insights from Hermansky‐Pudlak syndrome and other rare diseases

  2019cites this paper
• The cargo adaptor proteins RILPL2 and melanophilin co-regulate myosin-5a motor activity

  2019cites this paper
• 16-Kauren-2-beta-18,19-triol inhibits melanosome transport in melanocytes by down-regulation of melanophilin expression.

  2019cites this paper
• Rab and Arf proteins at the crossroad between membrane transport and cytoskeleton dynamics.

  2018cites this paper
• Myosin Va from Eriocheir sinensis: cDNA cloning, expression and involvement in growth and development.

  2018cites this paper
• RAB27B requirement for stretch-induced exocytosis in bladder umbrella cells.

  2018cites this paper
• Silencing Stem Cell Factor Gene in Fibroblasts to Regulate Paracrine Factor Productions and Enhance c-Kit Expression in Melanocytes on Melanogenesis

  2018cites this paper
• Toll‐like receptors 2 and 3 enhance melanogenesis and melanosome transport in human melanocytes

  2018cites this paper
• Consequences of Rab GTPase dysfunction in genetic or acquired human diseases

  2018cites this paper
• 36H: A Novel Potent Inhibitor for Antimelanogenesis

  2018cites this paper
• MicroRNA-5110 regulates pigmentation by cotargeting melanophilin and WNT family member 1

  2018cites this paper
• Miozyny niekonwencjonalne i ich rola w mięśniach poprzecznie prążkowanych i komórkach miogennych

  2018cites this paper
• Further evidence for genotype–phenotype disparity in Griscelli syndrome

  2017cites this paper
• The small GTPase, Rab27, and its effectors and regulators participate in granule exocytosis by parotid acinar cells

  2017cites this paper
• Myosin Va’s adaptor protein melanophilin enforces track selection on the microtubule and actin networks in vitro

  2017cites this paper
• Inefficient recruitment of kinesin-1 to melanosomes precludes it from facilitating their transport

  2017cites this paper
• Exophilin-8 assembles secretory granules for exocytosis in the actin cortex via interaction with RIM-BP2 and myosin-VIIa

  2017cites this paper
• Retinal Progenitor Cell, Induced Pluripotent Stem Cell, and 3D Mini Retina Derived Extracellular Vesicles Contain Transcription Factors, MicroRNA and Protein Associated with Potency and Development

  2017cites this paper
• Cross-talk between interferon-gamma and interleukin-18 in melanogenesis.

  2016cites this paper
• How peroxisomes partition between cells. A story of yeast, mammals and filamentous fungi.

  2016cites this paper
• Molecular regulation of insulin granule biogenesis and exocytosis.

  2016cites this paper
• Two pathways regulate cortical granule translocation to prevent polyspermy in mouse oocytes

  2016cites this paper
• Structural Basis of Cargo Recognition by Unconventional Myosins in Cellular Trafficking

  2016cites this paper
• PLEKHM1/DEF8/RAB7 complex regulates lysosome positioning and bone homeostasis.

  2016cites this paper
• Kinetic Adaptations of Myosins for Their Diverse Cellular Functions

  2016cites this paper
• Griscelli syndrome type-3

  2016cites this paper
• Myosin Va and Endoplasmic Reticulum Calcium Channel Complex Regulates Membrane Export during Axon Guidance.

  2016cites this paper