2021 Vol. 12, No. 7

Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. The work of Chen et al. suggests that SANPCs share dominant biological properties with glutamatergic neurons, and the glutamatergic neurotransmitter system may act as an intrinsic regulation module of heart rhythm, which provides a potential intervention target for pacemaker cell-associated arrhythmias.

Recollection
Shu-szi Sin: A Chinese pioneer biologist, ancient agronomist, and educator
Qun Xie, Yan-ping Cheng, Lei Fu
2021, 12(7): 515-517. doi: 10.1007/s13238-019-00657-x
Abstract:
Hightlight
Sinoatrial node pacemaker cells: cardiomyocyte-or neuron-like cells?
Bin Zhou
2021, 12(7): 518-519. doi: 10.1007/s13238-021-00827-w
Abstract:
Review
Lipids and membrane-associated proteins in autophagy
Linsen Li, Mindan Tong, Yuhui Fu, Fang Chen, Shen Zhang, Hanmo Chen, Xi Ma, Defa Li, Xiaoxia Liu, Qing Zhong
2021, 12(7): 520-544. doi: 10.1007/s13238-020-00793-9
Abstract:
Autophagy is essential for the maintenance of cellular homeostasis and its dysfunction has been linked to various diseases. Autophagy is a membrane driven process and tightly regulated by membrane-associated proteins. Here, we summarized membrane lipid composition, and membrane-associated proteins relevant to autophagy from a spatiotemporal perspective. In particular, we focused on three important membrane remodeling processes in autophagy, lipid transfer for phagophore elongation, membrane scission for phagophore closure, and autophagosome-lysosome membrane fusion. We discussed the significance of the discoveries in this field and possible avenues to follow for future studies. Finally, we summarized the membrane-associated biochemical techniques and assays used to study membrane properties, with a discussion of their applications in autophagy.
Short article
Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons
Dandan Liang, Zhigang Xue, Jinfeng Xue, Duanyang Xie, Ke Xiong, Huixing Zhou, Fulei Zhang, Xuling Su, Guanghua Wang, Qicheng Zou, Yi Liu, Jian Yang, Honghui Ma, Luying Peng, Chunyu Zeng, Gang Li, Li Wang, Yi-Han Chen
2021, 12(7): 545-556. doi: 10.1007/s13238-020-00820-9
Abstract:
Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca2+ transients frequency in single SANPC. Collectively, our work suggests that SANPCs share dominant biological properties with glutamatergic neurons, and the glutamatergic neurotransmitter system may act as an intrinsic regulation module of heart rhythm, which provides a potential intervention target for pacemaker cell-associated arrhythmias.
Research article
Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network
Yu-Kun Xia, Yi-Rong Zeng, Meng-Li Zhang, Peng Liu, Fang Liu, Hao Zhang, Chen-Xi He, Yi-Ping Sun, Jin-Ye Zhang, Cheng Zhang, Lei Song, Chen Ding, Yu-Jie Tang, Zhen Yang, Chen Yang, Pu Wang, Kun-Liang Guan, Yue Xiong, Dan Ye
2021, 12(7): 557-577. doi: 10.1007/s13238-020-00754-2
Abstract:
Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)- mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1- BAP1-TF in regulating target genes and leukemia cell growth.
Letters
Roles of Tet2 in meiosis, fertility and reproductive aging
Huasong Wang, Linlin Liu, Mo Gou, Guian Huang, Chenglei Tian, Jiao Yang, Haiying Wang, Qin Xu, Guo_Liang Xu, Lin Liu
2021, 12(7): 578-585. doi: 10.1007/s13238-020-00805-8
Abstract:
Repurposing FDA-approved drugs for SARS-CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction
Wenyu Fu, Yujianan Chen, Kaidi Wang, Aubryanna Hettinghouse, Wenhuo Hu, Jing-Quan Wang, Zi-Ning Lei, Zhe-Sheng Chen, Kenneth A. Stapleford, Chuan-ju Liu
2021, 12(7): 586-591. doi: 10.1007/s13238-020-00803-w
Abstract: