Distribution of plasma membrane-associated syntaxins 1 through 4 indicates distinct trafficking functions in the synaptic layers of the mouse retina

Sherry, David M.; Mitchell, Robert A.; Standifer, Kelly M.; Plessis, Brad du

doi:10.1186/1471-2202-7-54

Cited by 74 publications

(112 citation statements)

References 118 publications

(130 reference statements)

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“…Polyclonal antibodies against syntaxin-4 (Millipore AB5330, immunogen corresponding to amino acids 2–23 of rat or mouse syntaxin-4) were raised in rabbit and used at a dilution of 1:500. Specificity of this antibody has been shown by Western blots of mouse retina and brain, where it recognized a single band at the appropriate molecular weight [4]. Immunostaining with syntaxin-4 shows the same staining pattern in the outer plexiform layer of guinea pig [5] mouse, rat, rabbit [3, 4] macaque, and ground squirrel ([1, 2] and this study).…”

Section: Methodssupporting

confidence: 61%

“…Specificity of this antibody has been shown by Western blots of mouse retina and brain, where it recognized a single band at the appropriate molecular weight [4]. Immunostaining with syntaxin-4 shows the same staining pattern in the outer plexiform layer of guinea pig [5] mouse, rat, rabbit [3, 4] macaque, and ground squirrel ([1, 2] and this study). Preadsorption of the antibody with the corresponding control peptide blocked all staining in rabbit retina [3].…”

Section: Methodssupporting

confidence: 61%

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Specialized synaptic pathway for chromatic signals beneath S-cone photoreceptors is common to human, Old and New World primates

et al. 2014

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The distribution of the SNARE protein syntaxin-4 and the cation-chloride transporter NKCC were investigated in the outer plexiform layer of human retina using immunohistochemistry. Both proteins, which are proposed to be components of a GABA-mediated feedforward circuit from horizontal cells directly to bipolar cells, were enriched beneath S-cones. The expression pattern of syntaxin-4 was further analyzed in baboon and marmoset to determine if the synaptic specialization is common to primates. Syntaxin-4 was enriched beneath S-cones in both species which together with the human results indicates that this specialization may have evolved for the purpose of mediating unique color vision capacities that are exclusive to primates.

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Section: Methodssupporting

confidence: 61%

Section: Methodssupporting

confidence: 61%

Specialized synaptic pathway for chromatic signals beneath S-cone photoreceptors is common to human, Old and New World primates

et al. 2014

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“…The yeast plasma membrane syntaxin orthologs have a threonine at the equivalent position (Figures 1B and S1). Furthermore, T254-containing syntaxins could also function in non-synaptic secretions, such as syntaxin 2 in postsynaptic membrane trafficking [26] and Drosophila syntaxin 1A in cuticle secretion [23,28]. Nonetheless, the overall feature emerging from our analysis is that syntaxins with conserved isoleucine at the +7 layer appear to be selectively involved in regulated secretion at synapses or neurosecretory cells.…”

Section: Resultsmentioning

confidence: 99%

Modification of a Hydrophobic Layer by a Point Mutation in Syntaxin 1A Regulates the Rate of Synaptic Vesicle Fusion

et al. 2007

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Both constitutive secretion and Ca2+-regulated exocytosis require the assembly of the soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complexes. At present, little is known about how the SNARE complexes mediating these two distinct pathways differ in structure. Using the Drosophila neuromuscular synapse as a model, we show that a mutation modifying a hydrophobic layer in syntaxin 1A regulates the rate of vesicle fusion. Syntaxin 1A molecules share a highly conserved threonine in the C-terminal +7 layer near the transmembrane domain. Mutation of this threonine to isoleucine results in a structural change that more closely resembles those found in syntaxins ascribed to the constitutive secretory pathway. Flies carrying the I254 mutant protein have increased levels of SNARE complexes and dramatically enhanced rate of both constitutive and evoked vesicle fusion. In contrast, overexpression of the T254 wild-type protein in neurons reduces vesicle fusion only in the I254 mutant background. These results are consistent with molecular dynamics simulations of the SNARE core complex, suggesting that T254 serves as an internal brake to dampen SNARE zippering and impede vesicle fusion, whereas I254 favors fusion by enhancing intermolecular interaction within the SNARE core complex.

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“…In the rodent retina, this antibody selectively labels RGC dendritic arbors and post-synaptic terminals (Mojumder et al, 2008a, b; Okabe et al 1989; Sherry et al, 2006). Millipore (MAB362) also produces this monoclonal antibody.…”

Section: Methodsmentioning

confidence: 99%

Early microglia activation in a mouse model of chronic glaucoma

Bosco¹,

Steele²,

Vetter³

2011

J of Comparative Neurology

280

218

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Changes in microglial cell activation and distribution are associated with neuronal decline in the CNS, particularly under pathological conditions. Activated microglia converge on the initial site of axonal degeneration in human glaucoma, yet, their part in its pathophysiology remains unresolved. To begin with, it is unknown whether microglia activation precedes or is a late consequence of retinal ganglion cell (RGC) neurodegeneration. Here, we address this critical element in DBA/2J (D2) mice, an established model of chronic inherited glaucoma, using as a control the congenic substrain DBA/2J Gpnmb+/SjJ (D2G), which is not affected by glaucoma. We analyzed the spatial distribution and timecourse of microglial changes in the retina, as well as within the proximal optic nerve prior to and throughout ages when neurodegeneration has been reported. Exclusively in D2 mice, we detected early microglia clustering in the inner central retina and unmyelinated optic nerve regions, with microglia activation peaking by 3 months of age. Between 5 and 8 months of age, activated microglia persisted and concentrated in the optic disc, but also localized to the retinal periphery. Collectively, our findings suggest microglia activation is an early alteration in the retina and optic nerve in D2 glaucoma, potentially contributing to disease onset or progression. Ultimately, detection of microglial activation may have value in early disease diagnosis, while modulation of microglial responses may alter disease progression.

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Distribution of plasma membrane-associated syntaxins 1 through 4 indicates distinct trafficking functions in the synaptic layers of the mouse retina

Cited by 74 publications

References 118 publications

Specialized synaptic pathway for chromatic signals beneath S-cone photoreceptors is common to human, Old and New World primates

Specialized synaptic pathway for chromatic signals beneath S-cone photoreceptors is common to human, Old and New World primates

Modification of a Hydrophobic Layer by a Point Mutation in Syntaxin 1A Regulates the Rate of Synaptic Vesicle Fusion

Early microglia activation in a mouse model of chronic glaucoma

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