Myosin IXa Binds AMPAR and Regulates Synaptic Structure, LTP, and Cognitive Function

Folci, Alessandra; Murru, Luca; Vezzoli, Elena; Ponzoni, Luisa; Gerosa, Laura; Moretto, Edoardo; Longo, Fabiana; Zapata, Jonathan; Braida, Daniela; Pistillo, Francesco; Bähler, Martin; Francolini, Maura; Sala, Mariaelvina; Bassani, Silvia

doi:10.3389/fnmol.2016.00001

Cited by 38 publications

(42 citation statements)

References 33 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Netrin 1 attracts spinal interneurons to the ventral spinal cord, through Deleted in colorectal cancer (DCC), and prevents them from exiting the CNS via the DREZ [31]. A more recent study demonstrated that another member, Netrin 5 (Ntn5), which is expressed by BC cells, prevented motor neuron migration out of the CNS by repulsion, likely mediated by DCC receptors expressed by motor neurons [32]. …”

Section: Molecular Mechanisms Mediating Cell Segregation At Tzsmentioning

confidence: 99%

“…Intriguingly, in Ntn5 mutant mice, Garrett et al observed that the defects were mainly located rostrally. This heterogeneous distribution of the defects along the antero-posterior axis led the authors to suggest that BC cell-derived Netrin 5 might signal towards a specific subtype of motor neuron [32]. An alternative explanation for this spatial pattern is that the proteins cited above and involved in restricting motor neurons within the CNS might be expressed at different levels in the neural tube, following opposite gradients along the antero-posterior axis.…”

Section: Molecular Mechanisms Mediating Cell Segregation At Tzsmentioning

confidence: 99%

See 1 more Smart Citation

Livin’ On The Edge: glia shape nervous system transition zones

Fontenas¹,

Kucenas²

2017

Current Opinion in Neurobiology

View full text Add to dashboard Cite

The vertebrate nervous system is divided into two functional halves; the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which consists of nerves and ganglia. Incoming peripheral stimuli transmitted from the periphery to the CNS and subsequent motor responses created because of this information, require efficient communication between the two halves that make up this organ system. Neurons and glial cells of each half of the nervous system, which are the main actors in this communication, segregate across nervous system transition zones and never mix, allowing for efficient neurotransmission. Studies aimed at understanding the cellular and molecular mechanisms governing the development and maintenance of these transition zones have predominantly focused on mammalian models. However, zebrafish has emerged as a powerful model organism to study these structures and has allowed researchers to identify novel glial cells and mechanisms essential for nervous system assembly. This review will highlight recent advances into the important role that glial cells play in building and maintaining the nervous system and its boundaries.

show abstract

Section: Molecular Mechanisms Mediating Cell Segregation At Tzsmentioning

confidence: 99%

Section: Molecular Mechanisms Mediating Cell Segregation At Tzsmentioning

confidence: 99%

Livin’ On The Edge: glia shape nervous system transition zones

Fontenas¹,

Kucenas²

2017

Current Opinion in Neurobiology

View full text Add to dashboard Cite

show abstract

“…This model implies that the COR domain acts as a permanent dimerization device and that the stimulation of GTPase activity depends on reciprocal complementation of two Roc active sites 7 , 14 , 15 , 17 , 19 . Similar to the prokaryotic Roco proteins, various studies report that LRRK2 can also form dimers through its Roc-COR domain in vitro 15 , 20 – 22 , although some other studies suggest that the protein is mainly monomeric 23 . A number of recent results indicate that in vivo functional LRRK2 cycles between a predominantly monomeric kinase-inactive form in the cytosol and a dimeric kinase-active form at the plasma membrane 24 , 25 .…”

Section: Introductionmentioning

confidence: 99%

A homologue of the Parkinson’s disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover

et al. 2017

View full text Add to dashboard Cite

Mutations in LRRK2 are a common cause of genetic Parkinson’s disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 was proposed to act as a GTPase activated by dimerization (GAD), while recent reports suggest LRRK2 to exist under a monomeric and dimeric form in vivo. It is however unknown how LRRK2 oligomerization is regulated. Here, we show that oligomerization of a homologous bacterial Roco protein depends on the nucleotide load. The protein is mainly dimeric in the nucleotide-free and GDP-bound states, while it forms monomers upon GTP binding, leading to a monomer-dimer cycle during GTP hydrolysis. An analogue of a PD-associated mutation stabilizes the dimer and decreases the GTPase activity. This work thus provides insights into the conformational cycle of Roco proteins and suggests a link between oligomerization and disease-associated mutations in LRRK2.

show abstract

“…Experimental procedures were performed in accordance with the European Communities Council Directive (86/809/EEC) on the care and use of animals, and were approved by the Ethics Committees of the CNR Institute of Neuroscience in line with the ARRIVE guidelines (Kilkenny et al 2010 ). Brain slices were prepared as described in literature (Folci et al 2016 ) and transferred to oxygenated aCSF for 2 h prior to the experiments. aCSF contained 125.00 mM NaCl, 2.5 mM KCl, 1.25 mM NaH 2 PO 4 , 26 mM NaHCO 3 , and 25 mM glucose (all purchased from Sigma–Aldrich S.p.A., Italy).…”

Section: Methodsmentioning

confidence: 99%

Biosynthesis of glycerol phosphate is associated with long-term potentiation in hippocampal neurons

et al. 2016

Self Cite

View full text Add to dashboard Cite

IntroductionNeurons have a very high energy requirement, and their metabolism is tightly regulated to ensure delivery of adequate substrate to sustain neuronal activity and neuroplastic changes. The mechanisms underlying the regulation of neuronal metabolism, however, are not completely clear.ObjectiveThe objective of this study was to investigate the central carbon metabolism in neurons, in order to identify the regulatory pathways governing neuronal anabolism and catabolism.MethodsHere we first have applied MS-based endometabolomics to elucidate the metabolic dynamics in cultured hippocampal primary neurons. Using nanoLC-ESI-LTQ Orbitrap MS approach followed by statistical analysis, we measure the dynamics of uniformly labeled 13C-glucose entering neurons. We adapted the method by coupling offline patch-clamp setup with MS to confirm findings in vivo.ResultsAccording to non-parametric statistical analysis of metabolic dynamics, in cultured hippocampal neurons, the glycerol phosphate shuttle is active and correlates with the metabolic flux in the pentose phosphate pathway. In the hippocampus, glycerol-3-phosphate biosynthesis was activated in response to long-term potentiation together with the upregulation of glycolysis and the TCA cycle, but was inactive or silenced in basal conditions.ConclusionsWe identified the biosynthesis of glycerol-3-phosphate as a key regulator in mechanisms implicated in learning and memory. Notably, defects in enzymes linked with the glycerol phosphate shuttle have been implicated in neurological disorders and intellectual disability. These results could improve our understanding of the general mechanisms of learning and memory and facilitate the development of novel therapies for metabolic disorders linked with intellectual disability.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-1083-9) contains supplementary material, which is available to authorized users.

show abstract

Myosin IXa Binds AMPAR and Regulates Synaptic Structure, LTP, and Cognitive Function

Cited by 38 publications

References 33 publications

Livin’ On The Edge: glia shape nervous system transition zones

Livin’ On The Edge: glia shape nervous system transition zones

A homologue of the Parkinson’s disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover

Biosynthesis of glycerol phosphate is associated with long-term potentiation in hippocampal neurons

Contact Info

Product

Resources

About