T-cadherin is a regulator of blood vessel remodeling and angiogenesis, involved in adiponectin-mediated protective effects in the cardiovascular system and in skeletal muscles. GWAS study has previously demonstrated a SNP in the Cdh13 gene to be associated with hypertension. However, the role of T-cadherin in regulating blood pressure has not been experimentally elucidated. Herein, we generated Cdh13^∆Exon3 mice lacking exon 3 in the Cdh13 gene and described their phenotype. Cdh13^∆Exon3 mice exhibited normal gross morphology, life expectancy, and breeding capacity. Meanwhile, their body weight was considerably lower than of WT mice. When running on a treadmill, the time spent running and the distance covered by Cdh13^∆Exon3 mice was similar to that of WT. The resting blood pressure in Cdh13^∆Exon3 mice was slightly higher than in WT, however, upon intensive physical training their systolic blood pressure was significantly elevated. While adiponectin content in the myocardium of Cdh13^∆Exon3 and WT mice was within the same range, adiponectin plasma level was 4.37-fold higher in Cdh13^∆Exon3 mice. Moreover, intensive physical training augmented the AMPK phosphorylation in the skeletal muscles and myocardium of Cdh13^∆Exon3 mice as compared to WT. Our data highlight a critically important role of T-cadherin in regulation of blood pressure and stamina in mice, and may shed light on the pathogenesis of hypertension.

Adipose tissue renewal requires precise coordination of stem/progenitor cell proliferation, preadipocyte commitment, and terminal adipocyte differentiation. T-cadherin (CDH13), an atypical GPI-anchored cadherin, is expressed in adipose tissue and functions as a receptor for high-molecular-weight (HMW) adiponectin—a key adipokine produced by adipose tissue and involved in metabolic regulation. While T-cadherin is implicated in cardiovascular and metabolic homeostasis, its role in adipogenesis still remains poorly understood. In this study, we used the 3T3-L1 preadipocyte model to investigate the function of T-cadherin in adipocyte differentiation. We analyzed T-cadherin expression dynamics during differentiation and assessed how T-cadherin overexpression or knockdown affects lipid accumulation, expression of adipogenic markers, and key signaling pathways including ERK, PI3K–AKT, AMPK, and mTOR. Our findings demonstrate that T-cadherin acts as a negative regulator of adipogenesis. T-cadherin overexpression ensured a proliferative, undifferentiated cell state, delaying early adipogenic differentiation and suppressing both lipid droplet accumulation and the expression of adipogenic markers. In contrast, T-cadherin downregulation accelerated differentiation, enhanced lipid accumulation, and increased insulin responsiveness, as indicated by PI3K–AKT pathway activation at specific stages of adipogenesis. These results position T-cadherin as a key modulator of adipose tissue plasticity, regulating the balance between progenitor expansion and terminal differentiation, with potential relevance to obesity and metabolic disease.

Microtubules are present in all eukaryotes, and their spatial organization in the cells depends on the function of microtubule-organizing centers (MTOCs). Various organelles may act in this capacity, including the centrosome, Golgi, nuclear envelope, endosomes, and others. The molecular mechanisms that facilitate microtubule nucleation and/or anchoring at MTOCs are diverse. Many proteins can participate in these processes while localized to different MTOCs—either simultaneously on several or alternately on each of them. Here we studied the Golgi-associated protein JAKMIP2 in various cells using the methods of fluorescent multichannel confocal microscopy with subsequent image analysis via our own algorithm, transfection with a genetic construct encoding a fused protein of interest, and microtubule recovery monitoring during nocodazole washout. We demonstrated for the first time that JAKMIP2 is present on centrosomes in various cells. We also found that its abundance at this location is dependent on the cell cycle stage. Furthermore, we showed that an excess of JAKMIP2 specifically impairs centrosome function as a MTOC. Finally, our data indicates that exogenous JAKMIP2 slows down centrosomal microtubule nucleation and may also affect their anchoring. Our findings make a new contribution to the existing knowledge of the molecular mechanisms of the centrosome’s function as a MTOC.

Background/Objectives: The changes in the level of small GTPase ARL4C are associated with the initiation and progression of many different cancers. The content of ARL4C varies greatly between different tissues, and the induction of ARL4C expression leads to changes in cell morphology and proliferation. Although ARL4C can bind alpha-tubulin and affect intracellular transport, the role of ARL4C in the functioning of the tubulin cytoskeleton remained unclear. The aim of the present work is to study this role; Methods: The cells of the following lines were used for the experiments: HeLa (human cervical carcinoma), MCF7 (human breast cancer), U2OS (human osteosarcoma), Vero, BS-C-1, and COS7 (African green monkey kidney). The receptor activation by agonists followed by the preparation of cell lysates, electrophoresis, and immunoblotting, as well as cell fixation and immunofluorescent staining, were used to assess endogenous ARL4C/ABCA1 levels and the microtubule network morphology. The microtubule regrowth technique was performed to estimate the rate of microtubule nucleation, and the overexpression of different ARL4C constructs was used to affect ARL4C activity in the cells; Results: We showed that the changes in the endogenous ARL4C level or the ARL4C activity alter the microtubule nucleation process in the cells; Conclusions: small GTPase ARL4C may serve as one of the regulators of the microtubule nucleation process both in normal and cancer cells.

Adipose tissue renewal requires precise coordination of stem/progenitor cell prolifera-tion, preadipocyte commitment, and terminal adipocyte differentiation. T-cadherin (CDH13), an atypical GPI-anchored cadherin, is expressed in adipose tissue and functions as a receptor for high-molecular-weight (HMW) adiponectin—a key adipokine produced by adipose tissue and involved in metabolic regulation. While T-cadherin is implicated in cardiovascular and metabolic homeostasis, its role in adipogenesis still remains poorly understood. In this study, we used the 3T3-L1 preadipocyte model to investigate the function of T-cadherin in adipocyte differentiation. We analyzed T-cadherin expression dynamics during differentiation and assessed how T-cadherin overexpression or knockdown affects lipid accumulation, expression of adipogenic markers, and activation of key signaling pathways including ERK, PI3K–AKT, AMPK, and mTOR. Our findings demonstrate that T-cadherin acts as a negative regulator of adipogenesis. T-cadherin overexpression ensured a proliferative, undifferentiated cell state, suppressing lipid droplet accumulation and adipogenic marker expression. In contrast, T-cadherin downregulation accelerated differentiation, enhanced lipid accumulation, and increased insulin responsiveness, as indicated by elevated PI3K and phosphorylated AKT levels. These results position T-cadherin as a key modulator of adipose tissue plasticity, regu-lating the balance between progenitor expansion and terminal differentiation, with po-tential relevance to obesity and metabolic disease.