Novel function of β-arrestin2 in the nucleus of mature spermatozoa

Neuhaus, Eva M.; Mashukova, Anastasia; Barbour, Jon; Wolters, Dirk; Hatt, Hanns

doi:10.1242/jcs.03046

Cited by 61 publications

(58 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Arr3 is predominantly found out of the nucleus due to the presence of its two-leucine nuclear export signal (45). However, Neuhaus et al (46) reported Arr3 to be localized in the nucleus of HEK293 cells and mature spermatozoa. COX-1 is located in the endoplasmic reticulum and perinuclear membranes, whereas COX-2 resides predominantly in the perinuclear envelope (47).…”

Section: Pgds (Data Not Shown) Strong Growth Was Also Observed On Trpmentioning

confidence: 99%

An Interaction between L-prostaglandin D Synthase and Arrestin Increases PGD2 Production

Mathurin

Gallant

Germain

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

L-type prostaglandin synthase (L-PGDS) produces PGDProstaglandins (PGs) 5 are lipid mediators formed from arachidonic acid through the action of cyclooxygenases (COXs). COXs convert arachidonic acid released from the plasma membrane to an intermediate substrate, PGH 2 , which is metabolized by specific synthases to produce PGs like PGD 2 (1, 2). PGD 2 is involved in various physiological processes such as vasodilatation, bronchoconstriction (3), regulation of pain (4), and sleep (5) but is also implicated in inflammatory responses such as asthma (6) and atherosclerosis (7). PGD 2 was shown to exhibit anti-inflammatory properties as well, as increased levels of PGD 2 are observed during the resolution phase of inflammation (8 -10). Recent work by our group showed that PGD 2 displays anabolic properties in bone (11,12).There are two types of prostaglandin D 2 synthase (PGDS). The hematopoietic PGDS (H-PGDS) is glutathione-requiring (13) and is expressed mainly in mast cells (14), megakaryocytes (15), and T-helper 2 lymphocytes (16). The lipocalintype PGDS (L-PGDS), also called ␤-trace, is glutathione-independent and is expressed abundantly in the central nervous system (17, 18), the heart (19), the retina (20), and the genital organs (21). L-PGDS is also the only enzyme among the members of the lipocalin gene family and binds small lipophilic substances like retinoic acid (22), bilirubin (23), and gangliosides (24).The arrestin family consists of ubiquitously expressed arrestin-2 and -3 (also known as ␤-arrestin-1 and -2) and two retinal arrestins (25). Arrestin-2 and -3 are multifunctional molecules in addition to their well known role in desensitization and internalization of G protein-coupled receptors (26). The identification of numerous non-receptor binding partners has expanded their functions to protein ubiquitination, chemotaxis, apoptosis, mitogen-activated protein kinases activation (27, 28), osteoclastogenesis inhibition (29), and regulation of the interleukin 1 (IL-1) pathway (30).It is remarkable how very little is known about the interaction partners and the mechanisms regulating the activity of PG synthases considering their crucial physiological and pathological roles and the clinical problems associated with the long term use of COX inhibitors. Here we show that arrestin-3 interacts with L-PGDS and increases L-PGDS-mediated PGD 2 production. An arrestin-3 peptide was identified as capable of inducing PGD 2 production by L-PGDS. This is important because it shows that by identifying interacting partners of PG synthases we can not only further our understanding of the

show abstract

Section: Pgds (Data Not Shown) Strong Growth Was Also Observed On Trpmentioning

confidence: 99%

An Interaction between L-prostaglandin D Synthase and Arrestin Increases PGD2 Production

Mathurin

Gallant

Germain

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…They showed that the nuclear translocation of ␤-arrestin 2 is dependent on receptor phosphorylation and clathrin-mediated receptor endocytosis. Their data indicate that odorant-receptor-induced nuclear localization of ␤-arrestin 2 might play a role in the regulation of gene expression during the early processes of fertilization (Neuhaus et al, 2006). Both ␤-arrestin 1 and ␤-arrestin 2 thus seem to serve as nuclear messengers for GPCRs.…”

Section: ␤-Arrestins As Nuclear Messengersmentioning

confidence: 99%

“…In addition, GPCRs can affect gene expression through the ␤-arrestin-dependent signaling mechanisms described above. Recent work, however, indicates that ␤-arrestins can affect gene expression more directly -by entering the nucleus Neuhaus et al, 2006). In human embryonic kidney 293, HeLa and osteosarcomal cells, ␤-arrestin 1 appears to be present in both the nucleus and the cytoplasm whereas ␤-arrestin 2 is cytoplasmic at steady state (Oakley et al, 2000;Scott et al, 2002;Wang et al, 2003b).…”

Section: ␤-Arrestins As Nuclear Messengersmentioning

confidence: 99%

“…Neuhaus and colleagues recently observed that ␤-arrestin 2 translocates to the nucleus in response to the activation of hOR 17-4, a G-protein-coupled odorant receptor expressed in spermatozoa (Neuhaus et al, 2006). They showed that the nuclear translocation of ␤-arrestin 2 is dependent on receptor phosphorylation and clathrin-mediated receptor endocytosis.…”

Section: ␤-Arrestins As Nuclear Messengersmentioning

confidence: 99%

See 1 more Smart Citation

β-arrestin signaling and regulation of transcription

Pei

2007

Journal of Cell Science

231

200

View full text Add to dashboard Cite

β-arrestin 1 and β-arrestin 2 are well-known negative regulators of G-protein-coupled receptor (GPCR) signaling. Upon GPCR activation, β-arrestins translocate to the cell membrane and bind to the agonist-occupied receptors. This uncouples these receptors from G proteins and promotes their internalization, thus causing desensitization. However, accumulating evidence indicates that β-arrestins also function as scaffold proteins that interact with several cytoplasmic proteins and link GPCRs to intracellular signaling pathways such as MAPK cascades. Recent work has also revealed that, in response to activation of certain GPCRs, β-arrestins translocate from the cytoplasm to the nucleus and associate with transcription cofactors such as p300 and cAMP-response element-binding protein (CREB) at the promoters of target genes to promote transcription. They also interact with regulators of transcription factors, such as IκBα and MDM2, in the cytoplasm and regulate transcription indirectly. This β-arrestin-mediated regulation of transcription appears to play important roles in cell growth, apoptosis and modulation of immune functions.

show abstract

“…Although b-arrestin2 usually displays a cytoplasmic distribution caused by constitutive nuclear export, 36 it also undergoes active nuclear import and has been shown to accumulate in the nucleus after stimulation of the odorant GPCR hOR17-4 in spermatozoa. 37 In these cells, the nuclear accumulation of b-arrestin2 may be implicated in the control of gene expression during the early steps of fertilization. It is therefore possible that the translocation of b-arrestin2 to the CD34 1 cell nucleus regulates some of the For personal use only.…”

Section: Linmentioning

confidence: 99%

CXCR7 participates in CXCL12-induced CD34+ cell cycling through β-arrestin–dependent Akt activation

Torossian

Anginot

Chabanon

et al. 2014

Blood

View full text Add to dashboard Cite

Key Points• CXCR7 is a key actor of the cell cycling and survival promoting effect of CXCL12 on primary human CD34 In addition to its well-known effect on migration and homing of hematopoietic stem/ progenitor cells (HSPCs), CXCL12 chemokine also exhibits a cell cycle and survivalpromoting factor for human CD34 1 HSPCs. CXCR4 was suggested to be responsible for CXCL12-induced biological effects until the recent discovery of its second receptor, CXCR7. Until now, the participation of CXCR7 in CXCL12-induced HSPC cycling and survival is unknown. We show here that CXCL12 was capable of binding CXCR7 despite its scarce expression at CD34 1 cell surface. Blocking CXCR7 inhibited CXCL12-induced

show abstract

Novel function of β-arrestin2 in the nucleus of mature spermatozoa

Cited by 61 publications

References 46 publications

An Interaction between L-prostaglandin D Synthase and Arrestin Increases PGD2 Production

An Interaction between L-prostaglandin D Synthase and Arrestin Increases PGD2 Production

β-arrestin signaling and regulation of transcription

CXCR7 participates in CXCL12-induced CD34+ cell cycling through β-arrestin–dependent Akt activation

Contact Info

Product

Resources

About