Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals

Yang, Jun; Pawlyk, Basil; Wen, Xiao Hong; Adamian, Michael; Soloviev, Maria; Michaud, Norman; Zhao, Yun; Sandberg, Michael A.; Makino, Clint L.; Li, Tiansen

doi:10.1093/hmg/ddm047

Cited by 37 publications

(44 citation statements)

References 40 publications

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“…Previous studies have demonstrated that MPP4 deficiency leads to a loss of PSD95, VELI3, and PMCAs from photoreceptor ribbon synapses (Aartsen et al, 2006;Yang et al, 2007). Labeling of retinal cryosections from Mpp4 Ϫ/Ϫ mice with TMEM16B antibodies demonstrated absence of TMEM16B immunoreactivity in the OPL region (Fig.…”

Section: Tmem16b Interacts With Psd95 and Is Part Of A Presynaptic Prmentioning

confidence: 68%

“…Characterization of two independent MPP4-deficient mice lines has revealed relatively mild phenotypes with minor morphological abnormalities (Aartsen et al, 2006;Yang et al, 2007) and only slightly impaired signal transmission from rods to second-order neurons (Yang et al, 2007). This may be caused by compensatory changes in the expression and distribution of functionally related proteins.…”

Section: Discussionmentioning

confidence: 99%

“…This may be caused by compensatory changes in the expression and distribution of functionally related proteins. Concurrent changes in the expression and distribution of SERCA2, IP 3 RII, and recoverin in MPP4-deficient synaptic terminals have been attributed as adaptive responses to increased cytosolic Ca 2ϩ levels induced by PMCA loss (Yang et al, 2007). The TMEM16 family consists of 10 members in humans and mouse (Rock and Harfe, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we and others have described a presynaptic protein complex in photoreceptors consisting of the cytoplasmic adaptor proteins MPP4, PSD95, and VELI3 that may also include PMCAs and the Ca 2ϩ -binding protein recoverin (Stöhr et al, 2005;Aartsen et al, 2006;Yang et al, 2007;Förster et al, 2009). MPP4 appears to hold a key scaffolding function in the recruitment and assembly of this complex as mice lacking MPP4 are characterized by an absence of PSD95, VELI3, and PMCAs from the ribbon synapse (Aartsen et al, 2006;Yang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…MPP4 appears to hold a key scaffolding function in the recruitment and assembly of this complex as mice lacking MPP4 are characterized by an absence of PSD95, VELI3, and PMCAs from the ribbon synapse (Aartsen et al, 2006;Yang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals

Stöhr¹,

Heisig²,

Benz³

et al. 2009

J. Neurosci.

196

186

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Photoreceptor ribbon synapses release glutamate in response to graded changes in membrane potential evoked by vast, logarithmically scalable light intensities. Neurotransmitter release is modulated by intracellular calcium levels. Large Ca 2ϩ -dependent chloride currents are important regulators of synaptic transmission from photoreceptors to second-order neurons; the molecular basis underlying these currents is unclear. We cloned human and mouse TMEM16B, a member of the TMEM16 family of transmembrane proteins, and show that it is abundantly present in the photoreceptor synaptic terminals in mouse retina. TMEM16B colocalizes with adaptor proteins PSD95, VELI3, and MPP4 at the ribbon synapses and contains a consensus PDZ class I binding motif capable of interacting with PDZ domains of PSD95. Furthermore, TMEM16B is lost from photoreceptor membranes of MPP4-deficient mice. This suggests that TMEM16B is a novel component of a presynaptic protein complex recruited to specialized plasma membrane domains of photoreceptors. TMEM16B confers Ca 2ϩ -dependent chloride currents when overexpressed in mammalian cells as measured by halide sensitive fluorescent protein assays and whole-cell patch-clamp recordings. The compartmentalized localization and the electrophysiological properties suggest TMEM16B to be a strong candidate for the long sought-after Ca 2ϩ -dependent chloride channel in the photoreceptor synapse.

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Section: Tmem16b Interacts With Psd95 and Is Part Of A Presynaptic Prmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals

Stöhr¹,

Heisig²,

Benz³

et al. 2009

J. Neurosci.

196

186

View full text Add to dashboard Cite

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Molecular dynamics of photoreceptor synapse formation in the developing chick retina

Wahlin¹,

Moreira²,

Hu³

et al. 2007

J of Comparative Neurology

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The cellular and molecular mechanisms underlying photoreceptor synaptogenesis are poorly understood. Furthermore, a detailed picture of the molecular composition of photoreceptor synapses, or their subtypes, is not yet available, nor do we know what differences, if any, exist among those subtypes. To address these questions, we investigated temporal and spatial patterns of expression and assembly of photoreceptor presynaptic components during chick embryo retinal development and early posthatched life by using reverse transcriptase polymerase chain reaction (RT-PCR), dissociated retinal cells, laser-capture microdissection (LCM), immunocytochemistry and confocal microscopy. Immunocytochemistry in tissue sections and dissociated cells showed many similarities and few differences in the synaptic composition of rods and cone subtypes, which, however, were found to project to different strata within the outer plexiform layer. A striking finding was the precise timetable of expression of synaptic genes and proteins during synaptogenesis. Although mRNAs for some synaptic molecules appeared as early as embryonic day (ED) 5-8 (the time of inner retina synaptogenesis), others were undetectable before the time of onset of photoreceptor synaptogenesis on ED13, including CAST, rim2, synapsin-2, syntaxin-3, synaptotagmin, glutamate receptors -1, -4, and -5, homer-1 and -2, and tenascin-R. Most synaptic proteins in photoreceptors followed a similar sequence of expression: they were negative or weakly positive before ED13, appeared in inner segments between ED13 and ED15, became subsequently detectable in perinuclear and axonal regions, and by ED18 were assembled into synaptic terminals and became undetectable in the inner segments. The identity of the signals that regulate the coordinated expression of these synaptic components remains to be investigated. J. Comp. Neurol. 506:822-837, 2008 Indexing terms: synaptogenesis; cone; rod; presynaptic; postsynaptic; ribbonThe neural retina has a laminated structure, in which three nuclear layers (outer nuclear layer, inner nuclear layer, and ganglion cell layer) are separated by two synaptic layers (outer plexiform layer and inner plexiform layer). The outer nuclear layer consists of rod and cone photoreceptors, the inner nuclear layer contains the cell bodies of bipolar, horizontal and amacrine neurons and Mü ller glia, and the ganglion cell layer contains ganglion and displaced amacrine neurons. Synapses between photoreceptors and bipolar and horizontal neurons occur in the outer plexiform layer, and those between bipolar, amacrine, and ganglion neurons occur in the inner plexiform layer. This highly stereotyped laminar organization represents an advantage over other regions of the central nervous system for studies of synapse formation. This paper will focus on the development of the specialized "ribbon" synaptic terminals of photoreceptor cells, known as rod spherules and cone pedicles, and their contacts with postsynaptic processes from bipolar and horizontal neurons. Syn...

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Type 4 OFF cone bipolar cells of the mouse retina express calsenilin and contact cones as well as rods

Haverkamp

Specht

Majumdar

et al. 2007

J of Comparative Neurology

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Immunocytochemical discrimination of distinct bipolar cell types in the mouse retina is a prerequisite for analyzing retinal circuitry in wild-type and transgenic mice. Here we demonstrate that among the more than 10 anatomically defined mouse bipolar cell types, type 4 bipolar cells are specifically recognized by anti-calsenilin antibodies. Axon terminals in the inner plexiform layer are not readily identifiable because calsenilin is also expressed in a subset of amacrine and ganglion cells. In contrast, in the outer plexiform layer calsenilin immunoreactivity allows the analysis of photoreceptor to type 4 bipolar cell contacts. A dense plexus of calsenilin-positive dendrites makes several basal contacts at cone pedicles. An individual calsenilin-positive bipolar cell contacts five to seven cones. In addition, some calsenilin-positive dendrites contact rod photoreceptors. On average we counted 10 rod spherule contacts per type 4 bipolar cell, and approximately 10% of rods contacted type 4 bipolar cells. We suggest that type 4 bipolar cells, together with the recently described type 3a and b cells, provide an alternative and direct route from rods to OFF cone bipolar cells. In the Bassoon DeltaEx4/5 mouse, a mouse mutant that shows extensive remodeling of the rod system including sprouting of horizontal and rod bipolar cells into the outer nuclear layer due to impaired synaptic transmission, we found that in addition mixed-input (type 3 and 4) OFF bipolar cells sprout to ectopic sites. In contrast, true cone-selective type 1 and 2 OFF cone bipolar cells did not show sprouting in the Bassoon mouse mutant.

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Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals

Cited by 37 publications

References 40 publications

TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals

TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals

Molecular dynamics of photoreceptor synapse formation in the developing chick retina

Type 4 OFF cone bipolar cells of the mouse retina express calsenilin and contact cones as well as rods

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