Homer/Vesl Proteins and Their Roles in CNS Neurons

Ehrengruber, Markus U.; Kato, Akihiko; Inokuchi, Kaoru; Hennou, Sonia

doi:10.1385/mn:29:3:213

Cited by 66 publications

(49 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 B-D). In recent studies, various types of JMCs have been predicted in neurons; for example, Homer family proteins bind with both cell surface glutamate receptors and Ca 2ϩ release channels on the ER to generate neural JMCs (11). It may be that the standard electron microscope analysis cannot distinguish JP-mediated JMCs from those with different molecular components in neurons.…”

Section: Resultsmentioning

confidence: 99%

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Moriguchi

Nishi

Komazaki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Junctional membrane complexes (JMCs) composed of the plasma membrane and endoplasmic͞sarcoplasmic reticulum seem to be a structural platform for channel crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the sarcoplasmic reticulum membrane and binding with the plasma membrane in muscle cells. In this article, we report that mutant JP double-knockout (JP-DKO) mice lacking neural JP subtypes exhibited an irregular hindlimb reflex and impaired memory. Electrophysiological experiments indicated that the activation of small-conductance Ca 2؉ -activated K ؉ channels responsible for afterhyperpolarization in hippocampal neurons requires endoplasmic reticulum Ca 2؉ release through ryanodine receptors, triggered by NMDA receptor-mediated Ca 2؉ influx. We propose that in JP-DKO neurons lacking afterhyperpolarization, the functional communications between NMDA receptors, ryanodine receptors, and small-conductance Ca 2؉ -activated K ؉ channels are disconnected because of JMC disassembly. Moreover, JP-DKO neurons showed an impaired long-term potentiation and hyperactivation of Ca 2؉ ͞calmodulin-dependent protein kinase II. Therefore, JPs seem to have an essential role in neural excitability fundamental to plasticity and integrated functions.hippocampus ͉ learning and memory ͉ long-term potentiation ͉ ryanodine receptor ͉ SK channel F unctional communication between cell-surface and intracellular channels is an essential feature of excitable cells (1). During initiation of contraction in striated muscle cells, the activation of cell-surface dihydropyridine receptor (DHPRs) channels opens ryanodine receptors (RyRs) and triggers Ca 2ϩ release from the sarcoplasmic reticulum via either the ''Ca 2ϩ -induced Ca 2ϩ release'' or the ''voltage-induced Ca 2ϩ release'' mechanism (2). The functional couplings between the channels take place in junctional membrane complexes (JMCs), designated as the ''triad junction'' in skeletal muscle, ''diad'' in cardiac muscle, and ''peripheral coupling'' in immature striated and smooth muscles (3, 4). Recent studies indicated that junctophilin (JP) subtypes, namely JP-1-JP-4, contribute to JMC formation in muscle cells (5, 6). In JP-1 knockout mice with perinatal lethality, mutant skeletal muscle shows deficiency of triad junctions and insufficient contraction probably caused by impaired communication between DHPRs and RyRs (7). In JP-2 knockout embryos showing cardiac arrest, mutant cardiac myocytes exhibit deficiency of peripheral couplings and arrhythmic Ca 2ϩ signaling probably caused by functional uncoupling between DHPRs and RyRs (5). In the brain, both JP-3 and JP-4 are expressed in similar discrete neuronal sites and may collaboratively contribute to JMC formation (8, 9). However, the role of neural JP subtypes is largely unknown. Using knockout mice lacking both JP-3 and JP-4 (JP-DKO mice), we report their essential contributions to the tuning of excitability and plasticity in hippocampal pyramidal neurons. ResultsGeneration of JP-DKO Mice Bearing Lethality. JP-4 knockou...

show abstract

Section: Resultsmentioning

confidence: 99%

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Moriguchi

Nishi

Komazaki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…2). Such physical links between varied receptors in postsynaptic, perisynaptic and intracellular membranes may mediate precise control of glutamatergic synapse function and development (Xiao et al, 2000;Ehrengruber et al, 2004). In these chains, changes with development may involve NMDA receptors and MAGUKs, so that most of the early chains probably include NR2B-containing receptors and SAP102 (an association of the latter in these chains is based on yeast two-hybrid screens of GKAP - Kim et al, 1997; see also review by van Zundert et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Proteins associated with the PSD can organize into extensive chains beginning with a complex of glutamate receptor-MAGUK-GKAP that can link through GKAP to Shank-Homer and continue to metabotropic GluRs and other proteins Xiao et al, 2000;Wenthold et al, 2003;Ehrengruber et al, 2004). Also, Shank may link directly with the GluRs (mGluR1 and GluRδ2), and indirectly to AMPA receptors via GRIP Uemura et al, 2004).…”

Section: The Shank-homer-mglur Chainmentioning

confidence: 99%

“…Postsynaptic density (PSD) proteins are necessary for excitatory glutamatergic postsynaptic responses, and include scaffolding and functional elements that modulate/mediate signal transduction and trafficking of synaptic proteins (reviewed by Sheng and Kim, 2002;Wenthold et al, 2003;Bredt and Nicoll, 2003;Ehrengruber et al, 2004). In addition to glutamate receptors (GluRs) such as α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and Nmethyl-D-aspartate (NMDA) receptors, numerous other proteins associate with GluRs in the postsynaptic membrane and PSD.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

208

196

View full text Add to dashboard Cite

In glutamatergic synapses, glutamate receptors (GluRs) associate with many other proteins involved in scaffolding and signal transduction. The ontogeny of these postsynaptic density (PSD) proteins involves changes in their composition during development, paralleling changes in GluR type and function. In the CA1 region of the hippocampus, at postnatal day 2 (P2), many synapses already have a distinct PSD. We used immunoblot analysis, subcellular fractionation, and quantitative immunogold electron microscopy to examine the distribution of PSD proteins during development of the hippocampus. Synapses at P2 contained substantial levels of NR1 and NR2B and most GluRassociated proteins, including SAP102, SynGAP, the chain of proteins from GluRs/SAP102 through GKAP/Shank/Homer and metabotropic glutamate receptors, and the adhesion factors, cadherin, catenin, neuroligin, and Nr-CAM. Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors and CaMKII. Other components showed more moderate changes.

show abstract

“…Zif 268 encodes a zinc finger transcription factor that regulates a number of genes and has been implicated in a variety of neuroplastic processes (28). Homer 1 is a member of a family of scaffolding proteins (Homer/Vesl proteins) of the postsynaptic density that cluster and traffic glutamate receptors, link these to internal calcium stores, and play a role in various mechanisms of synapse structuring and plasticity (29,30,75). The homer 1 signal rapidly induced by psychostimulants (45,70,76) and other treatments mostly reflects the IEG isoform homer 1a (60).…”

Section: Altered Gene Expression In the Striatummentioning

confidence: 99%

Augmented D1 Dopamine Receptor Signaling and Immediate-Early Gene Induction in Adult Striatum After Prenatal Cocaine

Tropea

Guerriero

Willuhn

et al. 2008

Biological Psychiatry

View full text Add to dashboard Cite

Background-Prenatal exposure to cocaine can impede normal brain development triggering a range of neuroanatomical and behavioral anomalies that are evident throughout life. Mouse models have been especially helpful in delineating neuro-teratogenic consequences following prenatal exposure tococaine. The present study employed a mouse model to investigate alterations in D 1 dopamine receptor signaling and downstream immediate-early gene induction in the striatum of mice exposed to cocaine in utero.

show abstract

Homer/Vesl Proteins and Their Roles in CNS Neurons

Cited by 66 publications

References 66 publications

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Augmented D1 Dopamine Receptor Signaling and Immediate-Early Gene Induction in Adult Striatum After Prenatal Cocaine

Contact Info

Product

Resources

About

Homer/Vesl Proteins and Their Roles in CNS Neurons

Cited by 66 publications

References 66 publications

Functional uncoupling between Ca 2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Functional uncoupling between Ca 2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Augmented D1 Dopamine Receptor Signaling and Immediate-Early Gene Induction in Adult Striatum After Prenatal Cocaine

Contact Info

Product

Resources

About

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins