Cloning and Characterization of SLP3: a Novel Member of the Stomatin Family Expressed by Olfactory Receptor Neurons

Goldstein, Bradley J.; Kulaga, Heather; Reed, Randall R.

doi:10.1007/s10162-002-2039-5

Cited by 41 publications

(37 citation statements)

References 32 publications

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“…Tissues for immunofluorescence were harvested from mice perfused with PFA or Bouin's fixative, and 20-μm cryosections were cut from OB or OE. Primary antibodies used were as follows: BBS8 (rabbit, 1:100), γ-tubulin (mouse, 1:200; Abcam), acetylated tubulin (mouse, 1:1,000; Sigma), ACIII (rabbit, 1:1,000; Santa Cruz Biotechnology), ORI7 [guinea pig, 1:2,500; Y. Yoshihara (RIKEN Brain Science Institute, Saitama, Japan)], SLP3 (rabbit, 1:50) (20), lacZ (chicken, 1:500; Abcam), S100A5 (rabbit, 1:200) (24). Some primary antibodies (ORI7, lacZ) required antigen retrieval (5′ 100C in 10 mM Na citrate, pH 6.0).…”

Section: Methodsmentioning

confidence: 99%

“…To further explore the observed protein mislocalization in the dendritic knob and cilia of OSNs, we generated a fusion of enhanced green fluorescent protein (eGFP) to SLP3, a stomatin-like protein that is abundant in OSNs and enriched in the dendrite and dendritic knob (20). Knock-in of eGFP to the SLP3 endogenous locus (Fig.…”

Section: Loss Of Bbs8 Reduces Olfactory Sensitivity and Causes Structmentioning

confidence: 99%

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Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting

Tadenev

Kulaga

May-Simera

et al. 2011

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

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102

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Bardet-Biedl syndrome (BBS) is a pleiotropic, heterogeneous human disease whose etiology lies primarily in dysfunctional basal bodies and/or cilia. Both BBS patients and several BBS mouse models exhibit impaired olfactory function. To explore the nature of olfactory defects in BBS, a genetic ablation of the mouse Bbs8 gene that incorporates a fluorescent reporter protein was created. The endogenous BBS8 protein and reporter are particularly abundant in olfactory sensory neurons (OSNs), and specific BBS8 antibodies reveal staining in the dendritic knob in a shell-like structure that surrounds the basal bodies. Bbs8-null mice have reduced olfactory responses to a number of odorants, and immunohistochemical analyses reveal a near-complete loss of cilia from OSNs and mislocalization of proteins normally enriched in cilia. To visualize altered protein localization in OSNs, we generated a SLP3 eGFP knock-in mouse and imaged the apical epithelium, including dendritic knobs and proximal cilia, in ex vivo tissue preparations. Additionally, protein reagents that reflect the characteristic neuronal activity of each OSN revealed altered activity in Bbs8-null cells. In addition to previously known defects at the ciliary border, we also observed aberrant targeting of OSN axons to the olfactory bulb; axons expressing the same receptor display reduced fasciculation and project to multiple targets in the olfactory bulb. We suggest that loss of BBS8 leads to a dramatic and variable reduction in cilia, the essential signaling platform for olfaction, which alters the uniformity of responses in populations of OSNs expressing the same receptor, thereby contributing to the observed axon-targeting defects.ciliopathy | olfactory activity | protein trafficking B ardet-Biedl syndrome (BBS), a heterogeneous human disease, encompasses pleiotropic phenotypes including obesity, polydactyly, retinal degeneration, and renal anomalies. The disease, associated with mutations in at least 16 genes, shows complex inheritance. The BBS8 gene was identified via shared homology with BBS4 and was recognized to bear similarity to bacterial pilF; pilF is thought to be involved in the assembly of pili, which are thin, hairlike extensions on prokaryotic cells (1). This prompted the hypothesis that BBS is primarily a disease of the basal body, a microtubule-based modified centriole that nucleates the ciliary axoneme. Subsequent work supports this common etiology of BBS (2). Characterized BBS genes are highly conserved exclusively among ciliated eukaryotes, and most BBS proteins localize to the basal body, centrosome, and/or cilium in ciliated cell-culture models and in ciliated tissues. BBS proteins are not thought to be essential structural proteins as the basal body and cilium remain largely intact in most mutant BBS models (3-5). Disruption of individual BBS genes leads to defects in intraflagellar transport (IFT), a process essential for protein trafficking within the cilium (6-8).Recent studies have found that seven BBS proteins-BBS1, -2, -4, -5, -7, -8,...

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Section: Methodsmentioning

confidence: 99%

Section: Loss Of Bbs8 Reduces Olfactory Sensitivity and Causes Structmentioning

confidence: 99%

Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting

Tadenev

Kulaga

May-Simera

et al. 2011

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

Self Cite

102

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“…Clusters that included neuron-like outgrowth expressed several genes associated with the neuronal lineage, strongly expressing Ascl1, neurogenin 1 (Neurog1) and Neurod1, as well as other olfactory neuronal markers such as Omp and Stoml3 (Goldstein et al, 2003), in contrast to undifferentiated basal cell islands (Table 1). We have found that cultures derived from c-Kit…”

Section: Basal Cell Isolationmentioning

confidence: 99%

Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo

et al. 2016

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Olfactory epithelium (OE) has a lifelong capacity for neurogenesis due to the presence of basal stem cells. Despite the ability to generate short-term cultures, the successful in vitro expansion of purified stem cells from adult OE has not been reported. We sought to establish expansion-competent OE stem cell cultures to facilitate further study of the mechanisms and cell populations important in OE renewal. Successful cultures were prepared using adult mouse basal cells selected for expression of c-KIT. We show that c-KIT signaling regulates self-renewal capacity and prevents neurodifferentiation in culture. Inhibition of TGFβ family signaling, a known negative regulator of embryonic basal cells, is also necessary for maintenance of the proliferative, undifferentiated state in vitro. Characterizing successful cultures, we identified expression of BMI1 and other Polycomb proteins not previously identified in olfactory basal cells but known to be essential for self-renewal in other stem cell populations. Inducible fate mapping demonstrates that BMI1 is expressed in vivo by multipotent OE progenitors, validating our culture model. These findings provide mechanistic insights into the renewal and potency of olfactory stem cells.

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“…Furthermore, stomatin was shown to interact with acid-sensing ion channels and to alter their gating in mammalian cells [17]. Stomatins are the founding members of a family of proteins called stomatin-like proteins which include SLP-1, 2 and 3 [18,19]. A function has not yet been ascribed to these three proteins but it is known that SLP-2 is expressed in a range of mammalian tissues, notably the plasma membrane of erythrocytes [20].…”

Section: Introductionmentioning

confidence: 99%

SLP-2 negatively modulates mitochondrial sodium–calcium exchange

et al. 2010

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a b s t r a c tMitochondria play a major role in cellular calcium homeostasis. Despite decades of studies, the molecules that mediate and regulate the transport of calcium ions in and out of the mitochondrial matrix remain unknown. Here, we investigate whether SLP-2, an inner membrane mitochondrial protein of unknown function, modulates the activity of mitochondrial Ca 2+ transporters. In HeLa cells depleted of SLP-2, the amplitude and duration of mitochondrial Ca 2+ elevations evoked by agonists were decreased compared to control cells. SLP-2 depletion increased the rates of calcium extrusion from mitochondria. This effect disappeared upon Na + removal or addition of CGP-37157, an inhibitor of the mitochondrial Na + /Ca 2+ exchanger, and persisted in permeabilized cells exposed to a fixed cytosolic Na + and Ca 2+ concentration. The rates of mitochondrial Ca 2+ extrusion were prolonged in SLP-2 over-expressing cells, independently of the amplitude of mitochondrial Ca 2+ elevations. The amplitude of cytosolic Ca 2+ elevations was increased by SLP-2 depletion and decreased by SLP-2 over-expression. These data show that SLP-2 modulates mitochondrial calcium extrusion, thereby altering the ability of mitochondria to buffer Ca 2+ and to shape cytosolic Ca 2+ signals.

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Cloning and Characterization of SLP3: a Novel Member of the Stomatin Family Expressed by Olfactory Receptor Neurons

Cited by 41 publications

References 32 publications

Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting

Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting

Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo

SLP-2 negatively modulates mitochondrial sodium–calcium exchange

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