Expression of MUPP1 protein in mouse brain

Sitek, Barbara; Poschmann, Gereon; Schmidtke, Katja; Ullmer, Christoph; Maskri, Lyutha; Andriske, Michael; Stichel, Christine C.; Zhu, Xin-Ran; Luebbert, H

doi:10.1016/s0006-8993(03)02338-2

Cited by 31 publications

(36 citation statements)

References 26 publications

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“…Furthermore, the MT 1 /MUPP1 interaction may be regulated by the expression level of MUPP1 itself. Despite the widespread expression of MUPP1 in the brain (45) and at multiple peripheral sites, its expression may vary depending on the cellular context and different pathological conditions. For instance, human keratinocyte infection by papillomavirus HPV18 E6 has been shown to induce epithelial hyperplasia and massive down-regulation of MUPP1 by targeting MUPP1 to the proteasome (23,46,47).…”

Section: Discussionmentioning

confidence: 99%

The PDZ Protein Mupp1 Promotes Gi Coupling and Signaling of the Mt1 Melatonin Receptor

Guillaume

Daulat

Maurice

et al. 2008

Journal of Biological Chemistry

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The concept of organized networks has emerged in the field of cellular signaling in the last few years. Assembling the different partners in close proximity optimizes the spatial and temporal organization and the specificity of the cellular response. The assembly of these multimolecular complexes occurs through the interaction of modular domains recognizing their target counterparts. PDZ domains are widely spread modules exhibiting this function. Data bank exploration with SMART (1) identifies 584 PDZ domains in 328 different proteins in the human genome.G protein-coupled receptors (GPCRs) 5 constitute the largest family of membrane receptors, and many of the more than 750 members have been shown to interact with PDZ domain-containing proteins, either constitutively or upon agonist activation (2). Binding of PDZ proteins to GPCRs has been reported to primarily regulate subcellular localization, trafficking, and stability of receptors (3). For instance, binding of MUPP1 and syntrophins to the ␥-aminobutyric acid type B (GABA B ) receptor and the ␣ 1D -adrenergic receptor, respectively, significantly increases receptor stability (4, 5). In other cases, PDZ scaffolds determine the subcellular localization of GPCRs (6) and receptor endocytosis as shown for PSD-95 and the 5-HT 2A serotonin and ␤ 1 -adrenergic receptors (7,8). PDZ proteins, such as NHERF and hScrib, are also important for the recycling of receptors to the cell surface (9 -11).Binding of PDZ proteins to GPCRs also modulates receptor signaling by assembling proteins involved in signal transduction. NHERF family proteins are known to regulate the activity of the Na ϩ /H ϩ exchanger through association with NHERF-1 (12) and to form a ternary complex with phospholipase C␤3 and GPCRs, which enhances the signaling efficiency of the receptor-mediated activation of the phospholipase C␤/Ca 2ϩ pathway (13-15). Binding of GIPC (GAIP-interacting protein, COOH terminus) to the COOH terminus of the D3 dopamine and the ␤ 1 -adrenergic receptor (16) decreased G␣ i -mediated signaling of these receptors most likely through RGS19, which binds to GIPC (17). Further examples of PDZ scaffolds that regulate GPCR signaling include a ternary complex formation around the PDZ scaffold MAGI-3, which binds to the GPCR frizzled-4 and Ltap to regulate the JNK signaling cascade (18), as well as PDZ-domain-containing Rho guanine nucleotide exchange factors that interact with lysophosphatidic acid 1 and 2 receptors to activate RhoA (19).

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Section: Discussionmentioning

confidence: 99%

The PDZ Protein Mupp1 Promotes Gi Coupling and Signaling of the Mt1 Melatonin Receptor

Guillaume

Daulat

Maurice

et al. 2008

Journal of Biological Chemistry

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“…Mupp1 interacts with GABA B receptors and 5-HT 2C receptors via different PDZ domains, the 13th and 10th PDZ domains, respectively. Because GABA B receptors, 5-HT 2C receptors, and Mupp1 exhibit overlapping distribution in the brain (28,39), it is possible that Mupp1 might physically link GABA B and 5-HT 2C receptors together. Such interactions may serve to facilitate well known examples of cross-talk between GABA B and serotonin receptors (40 -42).…”

Section: Discussionmentioning

confidence: 99%

GABAB Receptor Association with the PDZ Scaffold Mupp1 Alters Receptor Stability and Function

Balasubramanian

Fam

Hall

2007

Journal of Biological Chemistry

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␥-Aminobutyric acid, type B (GABA B ) receptors are heterodimeric G protein-coupled receptors that mediate slow inhibitory synaptic transmission in the central nervous system. To identify novel interacting partners that might regulate GABA B receptor (GABA B R) functionality, we screened the GAB-A B R2 carboxyl terminus against a recently created proteomic array of 96 distinct PDZ (PSD-95/Dlg/ZO-1 homology) domains. The screen identified three specific PDZ domains that exhibit interactions with GABA B R2: Mupp1 PDZ13, PAPIN PDZ1, and Erbin PDZ. Biochemical analysis confirmed that full-length Mupp1 and PAPIN interact with GABA B R2 in cells. Disruption of the GAB-A B R2 interaction with PDZ scaffolds by a point mutation to the carboxyl terminus of the receptor dramatically decreased receptor stability and attenuated the duration of GABA B receptor signaling. The effects of mutating the GABA B R2 carboxyl terminus on receptor stability and signaling were mimicked by small interference RNA knockdown of endogenous Mupp1. These findings reveal that GABA B receptor stability and signaling can be modulated via GABA B R2 interactions with the PDZ scaffold protein Mupp1, which may contribute to cell-specific regulation of GABA B receptors in the central nervous system. GABA B2 receptors are G protein-coupled receptors responsible for mediating slow inhibitory synaptic transmission by the neurotransmitter GABA (1). They belong to G protein-coupled receptor Family C and bear a high degree of homology to other family members such as the metabotropic glutamate receptors, calcium receptor, and vomeronasal receptors. GABA B receptors are believed to be heterodimeric combinations of two G protein-coupled receptors, GABA B R1 and GABA B R2 (2-4). Heterodimerization of GABA B R1 and GABA B R2 is necessary for the proper trafficking of GABA B R1 to the cell surface (5, 6). In the context of the heterodimer, GABA B R1 is thought to bind the ligand (7), whereas GABA B R2 is believed to be the primary G protein contact site (8 -11).Given that GABA B receptors are important therapeutic targets for a wide variety of diseases, including depression, anxiety, epilepsy, and drug addiction (12, 13), understanding GABA B receptor signaling and regulation is of significant clinical interest. The cloning of the GABA B receptors has advanced the study of the GABA B receptors substantially over the past decade. However, some discrepancies between the properties of native GABA B receptors and heterologously expressed recombinant receptors still remain. For example, GABA B receptors in native tissue undergo robust endocytosis and desensitization (14), whereas recombinant GABA B R1/GABA B R2 expressed in most heterologous cells neither internalize nor desensitize (14, 15). One possible explanation for such discrepancies is that GABA B receptor signaling and trafficking properties are highly dependent on cellular context. This implies that interaction with differentially expressed cellular proteins might modulate GABA B receptor function. Indeed, we...

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“…In a recent report, we have shown that the Multi-PDZ domain protein MUPP1, which has 13 PDZ domain binding motifs (Ullmer et al, 1998;Sitek et al, 2003), is expressed in the acrosomal region of mammalian spermatozoa (Heydecke et al, 2006). In the present work, we address the question whether MUPP1 is present in detergent-resistant membrane (DRM) rafts isolated from mammalian spermatozoa, and whether it is functionally involved in acrosomal secretion.…”

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confidence: 94%

The Multi‐PDZ domain protein MUPP1 as a lipid raft‐associated scaffolding protein controlling the acrosome reaction in mammalian spermatozoa

Ackermann

Zitranski

Heydecke

et al. 2007

Journal Cellular Physiology

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The success of acrosomal exocytosis, a complex process with a variety of interrelated steps, relies on the coordinated interaction of participating signaling molecules. Since scaffolding proteins are known to spatially organize sequential signaling pathways, we examined whether the Multi-PDZ domain protein MUPP1, recently identified in mammalian spermatozoa, is functionally active in controlling acrosomal secretion in mammalian sperm cells. To address this question, permeabilized mouse sperm were loaded with inhibitory antibodies against MUPP1 as well as with a photosensitive Ca 2þ chelator which allows a controlled release of acrosomal Ca 2þ. The results revealed that MUPP1 controls initial tethering and docking of the acrosomal vesicle, whereas syntaxin 2, a t-SNARE protein also expressed in the acrosomal cap of mammalian spermatozoa, appears to take part in the final process of acrosomal fusion. Interestingly, using immunogold electron microscopy, it was found that MUPP1 is detectable in the region of the periacrosomal membrane. Furthermore, in isolated detergent-insoluble glycolipid-enriched membrane domains from epididymal spermatozoa, MUPP1 was found to show a striking association with the Triton X-100 insoluble membrane fraction, which did not change significantly upon sperm capacitation or partial chemical extraction of cholesterol. This evidence points to a role of MUPP1 as a membrane raft-associated molecular organizer, and suggests that mammalian spermatozoa may use a scaffolding protein and distinct membrane subdomains to spatially organize components involved in the process of acrosomal exocytosis.

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Expression of MUPP1 protein in mouse brain

Cited by 31 publications

References 26 publications

The PDZ Protein Mupp1 Promotes Gi Coupling and Signaling of the Mt1 Melatonin Receptor

The PDZ Protein Mupp1 Promotes Gi Coupling and Signaling of the Mt1 Melatonin Receptor

GABAB Receptor Association with the PDZ Scaffold Mupp1 Alters Receptor Stability and Function

The Multi‐PDZ domain protein MUPP1 as a lipid raft‐associated scaffolding protein controlling the acrosome reaction in mammalian spermatozoa

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