TY  - JOUR
A1  - Andreska, Thomas
A1  - Lüningschrör, Patrick
A1  - Wolf, Daniel
A1  - McFleder, Rhonda L.
A1  - Ayon-Olivas, Maurilyn
A1  - Rattka, Marta
A1  - Drechsler, Christine
A1  - Perschin, Veronika
A1  - Blum, Robert
A1  - Aufmkolk, Sarah
A1  - Granado, Noelia
A1  - Moratalla, Rosario
A1  - Sauer, Markus
A1  - Monoranu, Camelia
A1  - Volkmann, Jens
A1  - Ip, Chi Wang
A1  - Stigloher, Christian
A1  - Sendtner, Michael
T1  - DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons
T2  - Cell Reports
N2  - Highlights
• Dopamine receptor-1 activation induces TrkB cell-surface expression in striatal neurons
• Dopaminergic deficits cause TrkB accumulation and clustering in the ER
• TrkB clusters colocalize with cargo receptor SORCS-2 in direct pathway striatal neurons
• Intracellular TrkB clusters fail to fuse with lysosomes after dopamine depletion

Summary
Disturbed motor control is a hallmark of Parkinson’s disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats. DRD1 activation causes enhanced TrkB translocation to the cell surface and increased sensitivity for BDNF. In contrast, dopamine depletion in cultured dSPN neurons, 6-OHDA-treated rats, and postmortem brain of patients with PD reduces BDNF responsiveness and causes formation of intracellular TrkB clusters. These clusters associate with sortilin related VPS10 domain containing receptor 2 (SORCS-2) in multivesicular-like structures, which apparently protects them from lysosomal degradation. Thus, impaired TrkB processing might contribute to disturbed motor function in PD.
KW  - motor learning
KW  - cortico-striatal synapse
KW  - basal ganglia
KW  - direct pathway
KW  - DRD1
KW  - dSPN
KW  - BDNF
KW  - TrkB
KW  - synaptic plasticity
KW  - GPCR
Y1  - 2023
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/34993
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-349932
VL  - 42
IS  - 6
ER  -