ARL13B TRAFFICKING

Role of Arl13b in endocytic trafficking

 Coordinatore FACULDADE DE CIENCIAS MEDICAS DA UNIVERSIDADE NOVA DE LISBOA 

 Organization address address: CAMPO MARTIRES DA PATRIA 130
city: LISBOA
postcode: 1169 056

contact info
Titolo: Prof.
Nome: Miguel
Cognome: Seabra
Email: send email
Telefono: +351-21-880 3033
Fax: +351-21 885 1920

 Nazionalità Coordinatore Portugal [PT]
 Totale costo 100˙000 €
 EC contributo 100˙000 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-2009-RG
 Funding Scheme MC-IRG
 Anno di inizio 2009
 Periodo (anno-mese-giorno) 2009-10-01   -   2013-09-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    FACULDADE DE CIENCIAS MEDICAS DA UNIVERSIDADE NOVA DE LISBOA

 Organization address address: CAMPO MARTIRES DA PATRIA 130
city: LISBOA
postcode: 1169 056

contact info
Titolo: Prof.
Nome: Miguel
Cognome: Seabra
Email: send email
Telefono: +351-21-880 3033
Fax: +351-21 885 1920

PT (LISBOA) coordinator 100˙000.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

ciliary    membrane    primary    intracellular    small    uncovering    sorting    late    pathway    moreover    dextran    regulatory    structure    destined    play    endocytic    linked    endosomes    mutations    exocyst    found    recent    materials    disorders    cargo    effectors    surface    maintenance    actin    bound    protein    endosome    class    regulation    regulators    scientists    molecular    functions    myh    family    muscle    trafficking    vesicles    cell    cd    cilia    crucial    function    mhc    mechanisms    arl       recycling    enzyme   

 Obiettivo del progetto (Objective)

'To move cargo between specific membrane-bound intracellular compartments, eukaryotic cells have evolved numerous mechanisms of membrane trafficking regulation. We found that CD1a, an MHC Class I-like lipid antigen presenting molecule follows an endocytic recycling pathway similar to that used by MHC Class I and other cargo internalized independently of clathrin. In an attempt to discover new regulators of this pathway, we screened a shRNA library for changes in CD1a surface expression and we found that the small GTPase Arl13b could be involved in the regulation of endocytic trafficking. The knock-down of Arl13b caused the clustering of early endosomes and the accumulation in this organelle of recycling cargo, such as transferrin, and also cargo destined for late endosomes and lysosomes, such as dextran. Moreover, the recycling rate of CD1a was decreased when Arl13b was knocked-down. Together, these results indicate that Arl13b regulates a sorting step from the early/sorting endosome. Arl13b belongs to the Arf-like (Arl) family of small GTPases, which remains poorly characterized. By uncovering its function we will shed light on the regulatory functions of this family of proteins. Future studies will focus on finding Arl13b effectors, determining if Arl13b binds to the cytoskeleton like other Arls, and also establishing the role of this protein in the primary cilium, a structure where Arl13b localizes prominently.'

Introduzione (Teaser)

Transporting materials from outside the cell and subsequent intracellular trafficking is an important cell function. European researchers have investigated a new molecular player that also has a crucial role in cell cilia maintenance.

Descrizione progetto (Article)

Cilia, hair-like projections on the cell surface, play a range of roles in mammals including chemical sensation and signal transduction. An enzyme, ADP-ribosylation factor-like protein 13B (Arl13b) is known to play a role in cilia formation and their maintenance.

In humans, mutations in Arl13b cause Joubert Syndrome, a rare disorder that affects the cerebellum. Symptoms include lack of muscle tone and abnormal breathing patterns with moderate mental retardation.

Recent research has indicated that Arl13b may play a significant role in trafficking of materials in membrane-bound vesicles (endocytic trafficking). The EU-funded 'Role of Arl13b in endocytic trafficking' (ARL13B TRAFFICKING) project aimed to determine the functional and regulatory role of this guanosine-5'-triphosphate (GTP)ase enzyme.

Using gene silencing techniques, the project scientists found that Arl13b is likely to control a sorting step from the early endosome. Material destined for late endosomes such as dextran was found to accumulate in the absence of Arl13b. Moreover, the recycling of molecules dependent on this endocytic mechanism slowed down.

Looking for effectors or regulators of Arl13b, the team identified non-muscle myosin heavy chain IIA, or Myh9. Arl13b interacts with Myh9 to lock onto actin. An important scaffolding protein, actin is crucial for cilia function and endocytosis.

The scientists identified another effector for Arl13b, a subunit of the exocyst. Significantly, the exocyst complex is involved in tethering vesicles from the Golgi Apparatus and the endocytic recycling compartment. Recent research has shown that the exocyst is required for ciliogenesis and proper localisation of ciliary cargo. The researchers argue that this interaction is linked to regulation of ciliary cargo by Ar1l3b.

ARL13B TRAFFICKING research has discovered two major regulators of a protein important in many cell functions but particularly in cell cargo movement. Mutations of the protein cause disorders linked to primary cilia structure. Uncovering the molecular mechanisms could form the basis of targeted therapies for related disorders.

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