Biología y Biomedicina >
Centro de Biología Molecular Severo Ochoa (CBM) >
(CBM) Artículos >
Closed Access item Rab 11 regulates constitutive dopamine transporter trafficking and function in N2A neuroblastoma cells
|Authors:||Furmana, Cheryse A.|
Lo, Charles B.
Esteban, José A.
Gnegy, Margaret E.
|Keywords:||Rab, DAT: Dopamine transporter, Trafficking|
|Citation:||Neuroscience Letters 463: 78–81 (2009)|
|Abstract:||The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission which undergoes
constitutive and substrate-mediated trafficking to and from the membrane. Although, considerable
research has been done to elucidate the regulation of substrate-stimulated DAT trafficking, less is known
about which trafficking proteins are involved in constitutive DAT trafficking. Rab proteins are GTPases
known to regulate the trafficking of proteins to and from specific endocytic compartments. Rabs 8 and 11,
in particular, are involved in trafficking proteins from intracellular compartments to the plasma membrane.
In this study, we sought to determine whether Rabs 8 and 11 would modulate DAT activity and
trafficking in N2A neuroblastoma cells.We used Rab mutations known to confer constitutively active or
dominant negative activity of these proteins to investigate the role of Rab activity in constitutive DAT
trafficking and function.We found that constitutively active Rab 11 upregulates DAT function and surface
expression while neither the constitutively active nor the dominant negative mutant of Rab 8 had any
effect on DA uptake. Furthermore, immunofluorescence experiments revealed that dominant negative
Rab 11 overexpression results in decreased surface DAT indicating a necessary function of Rab 11 in DAT
trafficking to the plasma membrane. These data show for the first time a functional role of Rab proteins
in the constitutive recycling of DAT to the plasma membrane.|
|Publisher version (URL):||http://dx.doi.org/10.1016/j.neulet.2009.07.049|
|Appears in Collections:||(CBM) Artículos|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.