Properties of primary cilia in melanin-concentrating hormone receptor 1-bearing hippocampal neurons in vivo and in vitro

Kobayashi, Yuki; Okada, Tomoya; Miki, Daisuke; Sekino, Yuko; Koganezawa, Noriko; Shirao, Tomoaki; Diniz, Giovanne B.; Saito, Yumiko

doi:10.1016/j.neuint.2020.104902

Cited by 18 publications

(31 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The neurons of mammalian brain have primary cilium, which are rich in a series of G protein-coupled receptors (GPCRs). Through melanin-concentrating hormone receptor 1 (MCHR1), the length of cilium can be changed to regulate neuronal activity and physiological functions, so as to achieve feeding and memory tasks [ 45 ].…”

Section: Mechanobiology Of Bmscsmentioning

confidence: 99%

The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation

Sun

Yuan

et al. 2021

Cell Biosci

View full text Add to dashboard Cite

Bone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.

show abstract

Section: Mechanobiology Of Bmscsmentioning

confidence: 99%

The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation

Sun

Yuan

et al. 2021

Cell Biosci

View full text Add to dashboard Cite

show abstract

“…The MCH-MCHR1 system constitutes a powerful regulatory system associated with food intake, energy expenditure, mood, and the sleep-wake cycle (38). Rodent MCHR1 is preferentially located in the primary cilia of neurons in the Accepted Article olfactory tubercle, hypothalamus, accumbens, and hippocampal formation, with MCHR1 in the latter concentrated in CA1 and CA3 regions but not in the dentate gyrus (42)(43)(44).We have previously described that MCH-MCHR1 binding mediates cilia length shortening in four different cultures of ciliated cells, including human retinal pigmented epithelial RPE1 cells (hRPE1) exogenously expressing MCHR1, rat hippocampal dissociated and slice neurons, and human-induced pluripotent stem cell-derived cortical neurons (44)(45)(46). We also demonstrated that Gi/o-dependent Akt phosphorylation is a major contributor of the initial stage of MCH-induced primary cilia shortening, leading to a downstream depolymerization of cytoplasmic tubulin and actin polymerization (44,45,47).…”

Section: Accepted Articlementioning

confidence: 99%

“…The hippocampal cells prepared from Wistar rats at embryonic day 18 were dissociated by trypsin treatment and stored in liquid nitrogen until the day of use (44,50). For culturing, frozen hippocampal cells (now commercially available as SKY Neuron from AlzMed, Inc.) were thawed in a thermostat bath at Accepted Article 10% fetal bovine serum, 0.6% glucose, and 10 nM pyruvic acid was transferred drop-wise to the 50 ml tube containing hippocampal cells.…”

Section: Rat Primary Dissociated Hippocampal Culturesmentioning

confidence: 99%

“…Subsequent steps were performed in the same method as in Section 2.7. The brains of fasted mice were stained by the frozen section method (44,51). For AC3/MCHR1 staining in primary cilia, 8-μm sections were heated at 70°C for 20 min in Histo VT One for antigen retrieval and blocked with Blocking One Histo (Nacalai Tesque) for 5 min.…”

Section: Fasting Of Micementioning

confidence: 99%

“…7A). Lastly, we took advantage of some of our recent finding in vivo that MCHR1-positive cilia length in the hippocampal CA1 region was significantly shortened in fasted mice compared with that in fed mice (44). When compared with the fed mice, mRNA expression of both PDLIM5 and alpha-actinin 1/4 was upregulated in the CA1 region of the fasting mouse for 48 hr (5-fold and 1.5-2-fold, respectively) (PDLIM5: p < 0.001, actinin 1: p < 0.001, actinin 4: p = 0.0036) (Fig.…”

Section: Accepted Articlementioning

confidence: 99%

See 2 more Smart Citations

Ciliary GPCR‐based transcriptome as a key regulator of cilia length control

et al. 2021

Self Cite

View full text Add to dashboard Cite

The primary cilium is a plasma membrane-protruding sensory organelle that efficiently conveys signaling cascades in a highly ordered microenvironment. Its signaling is mediated, in part, by a limited set of GPCRs preferentially enriched in the cilium membrane. This includes melanin-concentrating hormone (MCH) receptor 1 (MCHR1), which plays a role in feeding and mood. In addition to its receptor composition, the length of the cilium is a characteristic parameter that is implicated in its function. We previously found that MCH can dynamically shorten cilia length via the Gi/o and Akt pathways in both MCHR1-expressing hTERT-RPE1 cells (hRPE1 cells) and rat hippocampal neurons. However, the detailed mechanisms by which MCH regulates cilia length through ciliary MCHR1 remains unclear. In this study, we aimed to determine the transcriptome changes in MCHR1-expressing hRPE1 cells in response to MCH to identify the target molecules involved in cilia length regulation via MCHR1 activation. RNA-sequencing analysis of ciliated cells subjected to MCH treatment showed upregulation of 424 genes and downregulation of 112 genes compared with static control cells. Validation by quantitative real-time PCR, knocking down, and CRISPR/Cas9-mediated knockout technology identified a molecule, PDZ and LIM domain-containing protein 5 (PDLIM5). Thus, it was considered as the most significant key factor for MCHR1-mediated shortening of cilia length. Additional analyses revealed that the actin-binding protein alpha-actinin 1/4 is a crucial downstream target of the PDLIM5 signaling pathway that exerts an effect on MCHR1-induced cilia shortening. In the endogenous MCHR1-expressing hippocampus, transcriptional upregulation of PDLIM5 and actinin 1/4, following the application of MCH, was detected when the MCHR1-positive cilia were shortened. Together, our transcriptome study based on ciliary MCHR1 function uncovered a novel and important regulatory step underlying cilia length control. These results will potentially serve as a basis for understanding the mechanism underlying the development of obesity and mood disorders.

show abstract

Large‐scale analysis reveals spatiotemporal circadian patterns of cilia transcriptomes in the primate brain

Baldi

Alhassen

Chen

et al. 2021

J of Neuroscience Research

View full text Add to dashboard Cite

Cilia are dynamic subcellular systems, with core structural and functional components operating in a highly coordinated manner. Since many environmental stimuli sensed by cilia are circadian in nature, it is reasonable to speculate that genes encoding cilia structural and functional components follow rhythmic circadian patterns of expression. Using computational methods and the largest spatiotemporal gene expression atlas of primates, we identified and analyzed the circadian rhythmic expression of cilia genes across 22 primate brain areas. We found that around 73% of cilia transcripts exhibited circadian rhythmicity across at least one of 22 brain regions. In 12 brain regions, cilia transcriptomes were significantly enriched with circadian oscil-

show abstract

Properties of primary cilia in melanin-concentrating hormone receptor 1-bearing hippocampal neurons in vivo and in vitro

Cited by 18 publications

References 60 publications

The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation

The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation

Ciliary GPCR‐based transcriptome as a key regulator of cilia length control

Large‐scale analysis reveals spatiotemporal circadian patterns of cilia transcriptomes in the primate brain

Contact Info

Product

Resources

About