Institut for Biomedicin

Christian Bjerggaard Vægter

ER EXPORT AND SURFACE TARGETING OF THE DOPAMINE TRANSPORTER ARE DEPENDENT ON THE DISTAL C-TERMINUS BUT OCCURS INDEPENDENTLY OF PDZ DOMAIN INTERACTIONS

Publikation: KonferencebidragPosterForskning

  • Christian Bjerggaard(Vægter)
  • Claus Loland, University of Copenhagen, Danmark
  • Hanne Hastrup, Columbia University, USA
  • Kenneth Madsen, University of Copenhagen, Danmark
  • Jonathan Javitch, Columbia University, USA
  • Ulrik Gether, University of Copenhagen, Danmark
  • Institut for Medicinsk Biokemi
The human dopamine transporter (hDAT) contains a type 2 C-terminal PDZ binding sequence, Leu-Lys-Val (LKV). It has been suggested that the interaction of this sequence with the "scaffolding" protein PICK1 is critical for surface targeting and presynaptic clustering of the transporter (Torres et al. Neuron 2001, 30:121-34). As expected, we find that deletion of the PDZ binding sequence (LKV) or substitution with three histidines resulted in retention of hDAT in the ER in both HEK293 and N2A neuroblastoma cells. However, substitution of LKV with the type 2 PDZ binding sequence SLL of the beta2- adrenergic receptor, which does not bind PICK1, did not affect membrane targeting. In addition, neither C-terminal addition of a tyrosine, an alanine nor the sequence RGS-6XHis affected significantly surface targeting of the hDAT. Since interactions with PDZ domains are dependent on the presence of a free C-terminal carboxylic acid, these data are inconsistent with involvement of such interactions in ER export/surface targeting of hDAT. Furthermore, progressive substitution of hDAT C-terminus with beta2- adrenergic receptor sequence beyond the tolerated C-terminal SLL-sequence caused intracellular retention suggesting that additional structural elements are critical for surface targeting of hDAT. We propose a dual function of the hDAT C-terminus involving non-PDZ domain interactions for ER export/surface targeting and PDZ-dependent interactions for e.g. presynaptic clustering
OriginalsprogEngelsk
Udgivelsesår2002
StatusUdgivet - 2002
BegivenhedSociety for Neuroscience 32nd annual meeting - Orlando, USA
Varighed: 2 nov. 20027 nov. 2002

Konference

KonferenceSociety for Neuroscience 32nd annual meeting
LandUSA
ByOrlando
Periode02/11/200207/11/2002

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