Colocalization of different neurotransmitter transporters on synaptic vesicles is sparse except for VGLUT1 and ZnT3

Upmanyu, N.; Jin, Jialin; Emde, Henrik von der; Ganzella, Marcelo; Bösche, Leon; Malviya, Viveka Nand; Zhuleku, Evi; Politi, Antonio Z.; Ninov, Momchil; Silbern, Ivan; Leutenegger, Marcel; Urlaub, Henning; Riedel, Dietmar; Preobraschenski, Julia; Milošević, Ira; Hell, Stefan W.; Jahn, Reinhard; Sambandan, Sivakumar

doi:10.1016/j.neuron.2022.02.008

Cited by 50 publications

(44 citation statements)

References 82 publications

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“…Finally, we applied MINSTED to the distribution of synaptic vesicles in a cultured rat hippocampal neuron, highlighted through tagging the protein synaptobrevin 2 with a primary/secondary antibody sandwich. The resulting MINSTED image displays fluorophore clusters of (38 ± 23) nm in diameter, in line with the expectation to represent vesicles 14 (Fig. 5j).…”

supporting

confidence: 86%

MINSTED nanoscopy enters the Ångström localization range

Weber¹,

Emde²,

Leutenegger³

et al. 2022

Preprint

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We report all-optical, room-temperature localization of fluorophores with precision in the Angstrom range. These precisions are attained in a STED microscope, by encircling the fluorophore with the low-intensity edge of the STED donut beam, while constantly increasing the absolute donut power. Individual fluorophores bound to a DNA strand are localized with σ = 4.7 Å, corresponding to a fraction of the fluorophore size, with only 2,000 detected photons. MINSTED fluorescence nanoscopy with single-digit nanometer resolution is exemplified by imaging nuclear pore complexes and the distribution of nuclear lamin in mammalian cells labeled by transient DNA hybridization. Since our experiments yield a localization precision σ = 2.3 Å, estimated for 10,000 detected photons, we anticipate that MINSTED will open up entirely new areas of application in the study of macromolecular complexes in cells.

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supporting

confidence: 86%

MINSTED nanoscopy enters the Ångström localization range

Weber¹,

Emde²,

Leutenegger³

et al. 2022

Preprint

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“…Research shows that nearly 36% of SVs carry two VTs, while the SV types containing vesicular glutamate transporter-1 (VGLUT1) and ZnT-3 account for the majority of multi-transporter vesicles (about 34% of all SVs). Co-localization of VGLUT1 and ZnT-3 increases the glutamate content of vesicles, resulting in an enhanced postsynaptic response [ 118 ]. The concentration of zinc in SVs is regulated by the activity dependence of glutamate mediated by ZnT-3 [ 119 , 120 ].…”

Section: Molecular Mechanism Of Zinc-associated Aging and Cognitive I...mentioning

confidence: 99%

“…Plasma and neurons depend on it to exchange through the blood vessel wall [117][118][119][120][123][124][125] ZnT-4…”

Section: Zinc Transportersmentioning

confidence: 99%

Zinc in Cognitive Impairment and Aging

et al. 2022

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Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable for the normal development of plants and for the normal growth of rats and birds. Zinc plays an important role in many physiological and pathological processes in normal mammalian brain development, especially in the development of the central nervous system. Zinc deficiency can lead to neurodegenerative diseases, mental abnormalities, sleep disorders, tumors, vascular diseases, and other pathological conditions, which can cause cognitive impairment and premature aging. This study aimed to review the important effects of zinc and zinc-associated proteins in cognitive impairment and aging, to reveal its molecular mechanism, and to highlight potential interventions for zinc-associated aging and cognitive impairments.

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“…However, it is known that individual neurons can release multiple transmitters from the same synapse 54 and recent research suggests co-release of dopamine and serotonin is functionally relevant, 55 although co-localisation of different neurotransmitter transporters is sparse. 56 As a consequence it is likely that the interplay between dopamine and serotonin in the striatum is important in motivational symptoms, as suggested by animal studies. 48,50 LED and antidepressant medication status were also incorporated into our modelling, with no effect on the interaction between DAT SBR and time.…”

Section: Limitationsmentioning

confidence: 99%

Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: Associations with apathy and anhedonia

Costello

Yamamori

Reeves

et al. 2022

Preprint

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Background Motivational symptoms such as apathy and anhedonia are common in Parkinson's disease, respond poorly to treatment, and have been hypothesised to share underlying neural mechanisms. Striatal dopaminergic dysfunction is considered central to motivational symptoms in Parkinson's disease, but the association has never been examined longitudinally. We investigated whether the progression of dopaminergic neurodegeneration was associated with emergent apathy and anhedonia symptoms in Parkinson's disease. Methods Longitudinal cohort study of 412 newly diagnosed Parkinson's disease patients followed over five years as part of the Parkinson's Progression Markers Initiative (PPMI) cohort. Apathy and anhedonia were measured using a composite score derived from relevant items of the 15-item geriatric depression scale (GDS-15) and part I of the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Dopaminergic neurodegeneration was measured using repeated ioflupane [123-I] single photon emission computed tomography imaging of striatal dopamine transporters (DAT). Results Linear mixed-effects modelling across all contemporaneous data points identified a significant negative relationship between striatal DAT specific binding ratio(SBR) and apathy/anhedonia symptoms, which emerged as Parkinson's disease progressed (interaction: β = -0.09, 95%CI[-0.15 -0.03], p=0.002). Appearance and subsequent worsening of apathy/anhedonia symptoms began on average two years after diagnosis and below a threshold striatal DAT SBR level. The interaction between striatal DAT SBR and time was specific to apathy/anhedonia symptoms, with no evidence of a similar interaction for general depressive symptoms from the GDS-15 (excluding apathy/anhedonia items) (β =-0.06, 95%CI[-0.13 0.01]) or motor symptoms indexed by the MDS-UPDRS part III (β =0.20, 95%CI[-0.25 0.65]). Conclusion The relationship between the progression of dopaminergic neurodegeneration and emergent apathy/anhedonia symptoms supports a central role for dopaminergic dysfunction in motivational symptoms in Parkinson's disease. Striatal DAT imaging may be a useful indicator of apathy/anhedonia risk that could inform intervention strategies.

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Colocalization of different neurotransmitter transporters on synaptic vesicles is sparse except for VGLUT1 and ZnT3

Cited by 50 publications

References 82 publications

MINSTED nanoscopy enters the Ångström localization range

MINSTED nanoscopy enters the Ångström localization range

Zinc in Cognitive Impairment and Aging

Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: Associations with apathy and anhedonia

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