PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12 myoblasts into myotubes

Ko, Ji‐Ae; Kimura, Yuichi; Matsuura, Kenji; Yamamoto, Hideaki; Gondo, Toshikazu; Inui, Makoto

doi:10.1242/jcs.03290

Cited by 35 publications

(56 citation statements)

References 33 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously showed that PDZRN3 is upregulated during myogenic and osteoblastic differentiation of C2C12 cells (8,11). The expression of PDZRN3 increases early (Ͻ12 h) after the induction of osteoblastic differentiation, whereas the protein is upregulated later (Ͼ48 h) after the induction of myogenic differentiation.…”

Section: Downregulation Of Pdzrn3 During Adipogenesis In 3t3-mentioning

confidence: 94%

“…Polyclonal antibodies to PDZRN3 were generated in rabbits and purified as described previously (11). Rabbit polyclonal antibodies to C/EBP␣ (sc-61), to STAT5a (sc-1081), and to JunB (sc-73); mouse monoclonal antibodies to C/EBP␤ (sc-7692), to PPAR␥ (sc-7233), and to STAT5b (sc-1656); and goat polyclonal antibodies to aP2 (sc8661) were obtained from Santa Cruz Biotechnology (Santa Cruz, CA).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, PDZRN3 was found to be downregulated during adipogenesis in 3T3-L1 cells. PDZRN3 has an inhibitory role in both osteoblastic and adipogenic differentiation, whereas it is essential for myogenic differentiation (8,11). Upregulation of PDZRN3 during osteoblastic differentiation is likely important for negative feedback control of the differentiation process, whereas downregulation of PDZRN3 appears to facilitate adipogenic differentiation.…”

Section: Downregulation Of Pdzrn3 During Adipogenesis In 3t3-mentioning

confidence: 99%

“…PDZRN3 and PDZRN4 constitute a subfamily of PDZRN proteins with two PDZ domains. PDZRN3 is expressed in a variety of human tissues including heart, skeletal muscle, liver, and brain (11). We previously showed that PDZRN3 is essential for myogenic differentiation of myoblasts into myotubes with the use of C2C12 mesenchymal progenitor cells (11).…”

mentioning

confidence: 99%

“…PDZRN3 is expressed in a variety of human tissues including heart, skeletal muscle, liver, and brain (11). We previously showed that PDZRN3 is essential for myogenic differentiation of myoblasts into myotubes with the use of C2C12 mesenchymal progenitor cells (11). PDZRN3 also regulates surface expression of the musclespecific receptor tyrosine kinase (MuSK) at the neuromuscular junction by functioning as a synapse-associated E3 ubiquitin ligase (12).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

Honda

Ishii

Inui

2013

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

, a member of the PDZRN (or LNX) family of proteins, is essential for the differentiation of mesenchymal stem cells into myotubes, but it plays an inhibitory role in the differentiation of these cells into osteoblasts. Given that mesenchymal stem cells also differentiate into adipocytes, we examined the possible role of PDZRN3 in adipogenesis in mouse 3T3-L1 preadipocytes. The expression of PDZRN3 decreased at both the mRNA and protein levels during adipogenic differentiation. RNAi-mediated depletion of PDZRN3 enhanced the differentiation of 3T3-L1 cells into adipocytes as assessed on the basis of lipid accumulation. The upregulation of aP2 and CCAAT/enhancerbinding protein (C/EBP)-␤ during adipocyte differentiation was also enhanced in the PDZRN3-depleted cells, as was the induction of peroxisome proliferator-activated receptor-␥ (PPAR␥), an upstream regulator of aP2 and C/EBP␣, at both the mRNA and protein levels. Among transcription factors that control the expression of PPAR␥, we found that STAT5b, but not STAT5a, was upregulated in PDZRN3-depleted cells at both mRNA and protein levels. Tyrosine phosphorylation of STAT5b, but not that of STAT5a, was also enhanced at an early stage of differentiation by PDZRN3 depletion. In addition, the expression of C/EBP␤ during the induction of differentiation was enhanced at the mRNA and protein levels in PDZRN3-depleted cells. Our results thus suggest that PDZRN3 negatively regulates adipogenesis in 3T3-L1 cells through downregulation of STAT5b and C/EBP␤ and consequent suppression of PPAR␥ expression. adipogenesis; C/EBP␤; differentiation; PDZRN3; PPAR␥; STAT5 THE PDZ (PSD-95/DISCS-LARGE ZO-1) domain mediates protein-protein interactions and thereby contributes to intracellular signaling. Members of the PDZ domain-containing RING finger (PDZRN or LNX) family of proteins share a common domain organization that includes an NH 2 -terminal RING domain, two or four PDZ domains in the central region, and a COOHterminal consensus motif for binding to the PDZ domain (9). PDZRN3 and PDZRN4 constitute a subfamily of PDZRN proteins with two PDZ domains. PDZRN3 is expressed in a variety of human tissues including heart, skeletal muscle, liver, and brain (11). We previously showed that PDZRN3 is essential for myogenic differentiation of myoblasts into myotubes with the use of C2C12 mesenchymal progenitor cells (11). PDZRN3 also regulates surface expression of the musclespecific receptor tyrosine kinase (MuSK) at the neuromuscular junction by functioning as a synapse-associated E3 ubiquitin ligase (12). On the other hand, PDZRN3 plays an inhibitory role in the differentiation of C2C12 cells into osteoblasts by suppressing Wnt signaling (8). In addition to mesenchymal stem cells, the expression of PDZRN3 was recently detected in the central nervous system of zebrafish including rhombomere 1, ventral retina, thalamus, and motor neurons, suggesting that the protein may also play a role during neural development (3).Mesenchymal stem cells differentiate into adipocytes in addition to myo...

show abstract

Section: Downregulation Of Pdzrn3 During Adipogenesis In 3t3-mentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Downregulation Of Pdzrn3 During Adipogenesis In 3t3-mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

Honda

Ishii

Inui

2013

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

PDZRN4 acts as a suppressor of cell proliferation in human liver cancer cell lines

Yang

Han

2015

Cell Biochemistry & Function

View full text Add to dashboard Cite

Recently, some reports show that Ligand of Numb Protein-X 1 (LNX1) could be a suppressor gene in gliomas, while our current research has firstly shown that PDZ domain containing ring finger 4 (PDZRN4), another member of LNX family, could also be a potential suppressor in hepatocellular carcinoma (HCC). PDZRN4, also named LNX4 (Ligand of Numb Protein-X 4), is a member of the LNX family. We recently found that PDZRN4, but not LNX1, was down-regulated in HCC samples, and the role of PDZRN4 in the progression of HCC had not been studied before. To address this question, firstly, we evaluated the expression of PDZRN4 in HCC samples and adjacent non-cancerous tissues. Semi-quantitative polymerase chain reaction showed that PDZRN4 was down-regulated in 24/36 (66.7%) HCC samples separately. In addition, our research shows that PDZRN4 is silenced in all of the 12 HCC cell lines tested. Subsequently, cell-based functional assay exhibited that ectopic expression of PDZRN4 inhibits the proliferation, plate colony formation and anchorage-independent colony formation of HCC cells. Collectively, our results showed that PDZRN4 might be a potential tumour suppressor gene and had anti-proliferative effect on HCC cell proliferation, which would be of great significance to the researches on HCC.

show abstract

PDZRN3 regulates differentiation of myoblasts into myotubes through transcriptional and posttranslational control of Id2

Honda

Inui

2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

PDZRN3 (also known as LNX3) is a member of the PDZ domain-containing RING finger protein family. We previously showed that PDZRN3 is essential for differentiation of myoblasts into myotubes and that depletion of PDZRN3 inhibits such differentiation downstream of the upregulation of myogenin, a basic helix-loop-helix (bHLH) transcription factor required for completion of the differentiation process. However, the mechanism by which PDZRN3 controls this process has remained unclear. Myogenin is rendered active during the late stage of myogenic differentiation by the downregulation of Id2, a negative regulator of bHLH transcription factors. We now show that depletion of PDZRN3 inhibits the differentiation of C2C12 cells by inducing the upregulation of Id2 and thereby delaying its downregulation. Knockdown of Id2 by RNA interference restores the differentiation of PDZRN3-depleted cells. Luciferase reporter assays revealed that a putative binding site for STAT5b in the Id2 gene promoter is required for the upregulation of Id2 expression by PDZRN3 depletion. In addition, the amount of phosphorylated Id2 was reduced and that of the nonphosphorylated protein concomitantly increased in PDZRN3-depleted cells, with the inhibitory effect of Id2 on bHLH transcription factors having previously been shown to be attenuated by phosphorylation of Id2 catalyzed by the complex of Cdk2 with cyclin A2 or E1. Indeed, the expression of cyclin A2, but not that of cyclin E1, was reduced in PDZRN3-depleted cells. Our results thus indicate that PDZRN3 plays a key role in the differentiation of myoblasts into myotubes by regulating Id2 at both transcriptional and posttranslational levels.

show abstract

PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12 myoblasts into myotubes

Abstract: Summary PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12 myoblasts into myotubes

Cited by 35 publications

References 33 publications

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

PDZRN4 acts as a suppressor of cell proliferation in human liver cancer cell lines

PDZRN3 regulates differentiation of myoblasts into myotubes through transcriptional and posttranslational control of Id2

Contact Info

Product

Resources

About