Dopamine transporter endocytic trafficking in striatal dopaminergic neurons: differential dependence on dynamin and the actin cytoskeleton.
PubMed Identifier: 24198373
author list: Gabriel LR, Wu S, Kearney P, Bellv? KD, Standley C, Fogarty KE, Melikian HE
has network: authors
has network: has subject area
published in: The Journal of neuroscience : the official journal of the Society for Neuroscience
has major subject area list: Corpus Striatum; Cytoskeleton; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Dynamins; Endocytosis
has minor subject area list: Animals; Cell Line, Tumor; Humans; Male; Mice; Protein Transport
information resource reference: Gabriel LR, Wu S, Kearney P, Bellv? KD, Standley C, Fogarty KE, Melikian HE. Dopamine transporter endocytic trafficking in striatal dopaminergic neurons: differential dependence on dynamin and the actin cytoskeleton. J Neurosci. 2013 Nov 06; 33(45):17836-46.
journal title abbreviation: J Neurosci
publication date: 2013-11-06T00:00:00
year: 2013
type: Academic Article
type: Article
type: Document
type: Information Resource
has subject area: Corpus Striatum
has subject area: Cytoskeleton
has subject area: Dopamine Plasma Membrane Transport Proteins
has subject area: Dopaminergic Neurons
has subject area: Dynamins
has subject area: Endocytosis
has subject area: Animals
has subject area: Cell Line, Tumor
has subject area: Humans
has subject area: Male
has subject area: Mice
has subject area: Protein Transport
authors: Authorship 52246
authors: Authorship 17505

Faculty Rank
type: Class

full name
tag name: prns:fullName
type: DatatypeProperty

author list
tag name: prns:hasAuthorList
type: DatatypeProperty

has faculty rank
tag name: prns:hasFacultyRank
type: ObjectProperty

has network
tag name: prns:hasNetwork
type: ObjectProperty

published in
tag name: prns:hasPublicationVenue
type: DatatypeProperty

has major subject area list
tag name: prns:hasSubjectAreaMajorTopicList
type: DatatypeProperty

has minor subject area list
tag name: prns:hasSubjectAreaMinorTopicList
type: DatatypeProperty

information resource reference
tag name: prns:informationResourceReference
type: DatatypeProperty

is primary position
tag name: prns:isPrimaryPosition
type: DatatypeProperty

latitude
tag name: prns:latitude
type: DatatypeProperty

longitude
tag name: prns:longitude
type: DatatypeProperty

photo
tag name: prns:mainImage
type: ObjectProperty

maximum weight
tag name: prns:maxWeight
type: DatatypeProperty

journal title abbreviation
tag name: prns:medlineTA
type: DatatypeProperty

MeSH DescriptorUI
tag name: prns:meshDescriptorUI
type: DatatypeProperty

MeSH semantic group name
tag name: prns:meshSemanticGroupName
type: DatatypeProperty

minimum weight
tag name: prns:minWeight
type: DatatypeProperty

number of authors
tag name: prns:numberOfAuthors
type: DatatypeProperty

number of connections
tag name: prns:numberOfConnections
type: DatatypeProperty

number of publications
tag name: prns:numberOfPublications
type: DatatypeProperty

Person ID
tag name: prns:personId
type: DatatypeProperty

person in primary position
tag name: prns:personInPrimaryPosition
type: ObjectProperty

position in department
tag name: prns:positionInDepartment
type: ObjectProperty

position in division
tag name: prns:positionInDivision
type: ObjectProperty

predicate node
tag name: prns:predicateNode
type: ObjectProperty

publication date
tag name: prns:publicationDate
type: DatatypeProperty

sort order
tag name: prns:sortOrder
type: DatatypeProperty

uniqueness weight
tag name: prns:uniquenessWeight
type: DatatypeProperty

year
tag name: prns:year
type: DatatypeProperty

Post Docs
tag name: umass:PostDocs
type: DatatypeProperty

Rotation Projects
tag name: umass:Rotation
type: DatatypeProperty

Academic Article
type: Class

Article
type: Class

Document
type: Class

PubMed Identifier
tag name: bibo:pmid
type: DatatypeProperty

author rank in publication
tag name: vivo:authorRank
type: DatatypeProperty
type: FunctionalProperty

Authorship
type: Class

Department
type: Class

Division
type: Class

has subject area
tag name: vivo:hasSubjectArea
type: ObjectProperty

HR job title
tag name: vivo:hrJobTitle
type: DatatypeProperty

Information Resource
type: Class

authors
tag name: vivo:informationResourceInAuthorship
type: ObjectProperty

linked author
tag name: vivo:linkedAuthor
type: ObjectProperty

linked information resource
tag name: vivo:linkedInformationResource
type: ObjectProperty

Position
type: Class

position in organization
tag name: vivo:positionInOrganization
type: ObjectProperty

preferred title
tag name: vivo:preferredTitle
type: DatatypeProperty
type: FunctionalProperty

predicate
tag name: rdf:predicate
type: ObjectProperty

type
tag name: rdf:type
type: ObjectProperty

label
tag name: rdfs:label
type: DatatypeProperty

Concept
type: Class

Agent
type: Class

first name
tag name: foaf:firstName
type: DatatypeProperty
type: FunctionalProperty

last name
tag name: foaf:lastName
type: DatatypeProperty
type: FunctionalProperty

Organization
type: Class

Person
type: Class

Protein Transport
MeSH DescriptorUI: D021381
MeSH semantic group name: Physiology
number of authors: 158
number of publications: 401
uniqueness weight: 0.881682
type: Concept

Endocytosis
MeSH DescriptorUI: D004705
MeSH semantic group name: Physiology
number of authors: 85
number of publications: 152
uniqueness weight: 0.912578
type: Concept

Humans
MeSH DescriptorUI: D006801
MeSH semantic group name: Living Beings
number of authors: 2672
number of publications: 63281
uniqueness weight: 0.148786
type: Concept

Authorship 52246
type: Authorship
linked information resource: Dopamine transporter endocytic trafficking in striatal dopaminergic neurons: differential dependence on dynamin and the actin cytoskeleton.

Animals
MeSH DescriptorUI: D000818
MeSH semantic group name: Living Beings
number of authors: 1197
number of publications: 20631
uniqueness weight: 0.27535
type: Concept

Mice
MeSH DescriptorUI: D051379
MeSH semantic group name: Living Beings
number of authors: 799
number of publications: 10827
uniqueness weight: 0.373141
type: Concept

Male
MeSH DescriptorUI: D008297
MeSH semantic group name: Physiology
number of authors: 2224
number of publications: 29804
uniqueness weight: 0.227993
type: Concept

Cytoskeleton
MeSH DescriptorUI: D003599
MeSH semantic group name: Anatomy
number of authors: 67
number of publications: 138
uniqueness weight: 0.936996
type: Concept

Dynamins
MeSH DescriptorUI: D034281
MeSH semantic group name: Chemicals & Drugs
number of authors: 9
number of publications: 10
uniqueness weight: 0.995094
type: Concept

Corpus Striatum
MeSH DescriptorUI: D003342
MeSH semantic group name: Anatomy
number of authors: 38
number of publications: 97
uniqueness weight: 0.934249
type: Concept

Dopamine Plasma Membrane Transport Proteins
MeSH DescriptorUI: D050483
MeSH semantic group name: Chemicals & Drugs
number of authors: 11
number of publications: 34
uniqueness weight: 0.957635
type: Concept

Cell Line, Tumor
MeSH DescriptorUI: D045744
MeSH semantic group name: Anatomy
number of authors: 372
number of publications: 1465
uniqueness weight: 0.727904
type: Concept

Neurobiology
type: Department
type: Organization

UMass Chan Medical School
type: Organization

Melikian, Haley
first name: Haley
last name: Melikian
full name: Haley E Melikian PhD
has faculty rank: Professor
latitude: 42.27737440000000
longitude: -71.76346650000000
photo: https://profiles.umassmed.edu/profile/Modules/CustomViewPersonGeneralInfo/PhotoHandler.ashx
Person ID: 302
person in primary position: Professor
type: Agent
type: Person
Post Docs: The Melikian Lab seeks a creative and motivated PhD neurobiologist to join our investigative team to study the mechanisms that govern addictive and motivated behaviors, with a focus on circuits that converge on and modulate dopaminergic terminals. We leverage intersectional approaches spanning from molecules to behavior, and utilize mouse genetic, viral, optogenetic and photometric methods. We are seeking postdoctoral applicants with a strong track record of productivity, who will take the lead on a novel project. Applicants will optimally have experience in mouse handling and modern neurobiology approaches (e.g. optogenetics, photometry), but other strong candidates will also be considered. The Neurobiology Department at UMASS Chan Medical School is the hub of a vibrant multidisciplinary neuroscience community, with research strengths in neuropsychiatric disorders, neurodegeneration, neuroinflammation, neuroplasticity, and neurodevelopment. Under the leadership of our recently appointed Chair, Dr. Danny Winder, the department provides an exceptional and interactive training environment that emphasizes team science in a diverse and inclusive space. Interested applicants should submit a CV and names of three references to Dr. Melikian: haley(dot)melikian(at)umassmed(dot)edu.
Rotation Projects: Potential Rotation Projects 1. Dopamine Transporter (DAT) Trafficking in Cocaine Addiction DAT is a membrane protein in dopamine (DA) axon teminals whose primary function is to remove released dopamine and thereby terminate synpatic transmission. Addictive psychostimulants, such as cocaine, block DAT function, which increases extracellular DA and is responsible for cocaine's addictive properties. DAT is not static at the plasma membrane, but is dynamically regulated by membrane traffficking. This project is to determine whether DAT membrane trafficking is required for cocaine addiction. Our lab has developed a novel, AAV-mediated, in vivo molecular replacement strategy, that replaces wildytpe DAT with DAT trafficking dysregulated mutants in adult mice. There are 2 possible rotation projects: Project 1a: Rotation students will assist in behaviorally assessing replacement mice as compared to controls, and will additionally use immumohistochemical approaches to validate mutant protein expression in dopamine neurons in situ. Students will gain experience in mouse behavior, brain dissection, preparation of brain slices, and immunhistochemical techniques in mouse brain. Project 1b: Rotation students will develop a CRISPR/Cas9 guide RNA in order to perform gene editing and mutate DAT in vivo, and will test its efficacy in vitro. Students will learn guide RNA design, and mammalian tissue culture, and genomic sequencing. Cocaine's Synaptic Actions at the Dopamine Transporter. Synaptic models. (A) Dopamine released into the extracellular space is rapidly cleared by the dopamine transporter (purple), thereby limiting the postsynaptic dopamine signal. (B) Cocaine binds to and blocks the dopamine transporter, allowing dopamine to accumulate extracellularly and enhancing the postsynaptic signal.
Rotation Projects: 2. Modulatory glutamate signaling: impact on motor function, novelty, and cocaine addiction Glutamate is the major excitatory neurotransmitter in the brain, but also has a modulatory role by signaling through metabotropic glutamate receptors (mGluRs). Recent work from our laboratory revealed that mGluR5 expression in DA neurons is required for DA signaling and several DA-dependent behaviors including motor learning and cocaine reward. However, the circuit- and mechanistic-specific underpinnings of these processes are unkonwn. Using a novel conditional knockout model, we are leveraging genetically encoded DA sensors to determine how DAergic mGluR5 impacts DA neuron function and DA-dependent behaviors in mice. Rotation students will learn to behaviorally assess cocaine addiction in this mouse model, and will learn immunohistochemical approaches to validate viral expression Cocaine Fails to increase DA in mGluR5-DA-silenced mice. Fiber photometry using genetically-encoded DA sensors during cocaine response. Control or mGluR5-DA-silenced mice were injected with 7.5 mg/kg cocaine and DA signals were recorded in the nucleus accumbens using dLight 1.2 sensor. Control mice: Cocaine caused a significant increase in the total DA signal from 3-5 min post-injection as compared to saline-injections. mGluR5-DA-silenced mice: Cocaine failed to significantly increase DA signals. *p<0.05, paired Student's t test, n=4-5.
Rotation Projects: 3. Nociceptin: A neuropeptide that impacts cocaine sensitivity Nociceptin is an endogenous opiate-like neuropeptide that is implicated in pain and reward motivation. Recent studies suggest that nociceptin has the capacity to block cocaine's initial addictive properties, but the mechanisms underlying nociceptin's actions are largely unknown. Work in our lab has discovered that nociceptin blocks cocaine reward, and does so by acting directly on DA axon terminals in the nucleus accumbens, the brain's "reward center". In addition, our results suggest that nociceptin likely shifts cocaine sensitivity, and does so by controlling reward tone differentially in males vs. females. These exciting results may pave the way towards harnesing nociceptin signaling as a potential addiction therapeutic. However, the mechanisms underlying nociceptin's actions are unknown, nor is it known whether nociceptin specificallly impacts cocaine reward, or other drugs of abuse. There are two possible rotation projects: Project 3a: Impact of nociceptin signaling on other drugs of abuse. Students will conduct addiction behavioral assays while infusing nociceptin directly into the nucleus accumbens in mice. Students will learn mouse handling and stereotaxic surgery, and mouse behavioral assays. Project 3b: Sex-specific differences in nociceptin signalig. Students will use RT-qPCR to test whether males and female mouse midbrain neurons express differing amounts of the nociceptin receptor, NOPR. Students will learn mouse handling skills, brain harvesting, and RT-qPCR. Nociceptin infusion into the nucleus accumbens blocks cocaine preference in females. Conditioned Place Preference Assay (CPP). Wildtype female mice received either saline or 10mg/kg cocaine (I.P.) and were trained for 3 days in a 3-chambered CPP aparatus, while being infused with either vehicle or 500nM nociceptin. Preference scores were determined on test days. Control-infused mice exhibited signifiant preference to the cocaine-paired…
preferred title: Professor

Authorship 17505
type: Authorship
author rank in publication: 7
linked author: Melikian, Haley
linked information resource: Dopamine transporter endocytic trafficking in striatal dopaminergic neurons: differential dependence on dynamin and the actin cytoskeleton.

Dopaminergic Neurons
MeSH DescriptorUI: D059290
MeSH semantic group name: Anatomy
number of authors: 16
number of publications: 38
uniqueness weight: 0.958768
type: Concept

Professor
sort order: 3
type: Faculty Rank

Professor
is primary position: true
position in department: Neurobiology
position in division: https://profiles.umassmed.edu/profile/15590085
sort order: 1
type: Position
HR job title: Professor
position in organization: UMass Chan Medical School

authors
maximum weight: 0.43182
minimum weight: 0.21591
number of connections: 2
predicate node: https://profiles.umassmed.edu/profile/1533
predicate: authors
type: Network

has subject area
maximum weight: 1
minimum weight: 0.25
number of connections: 12
predicate node: https://profiles.umassmed.edu/profile/42
predicate: has subject area
type: Network