Swamy Harsha, Glading Angela J
Department of Pharmacology and Physiology, University of Rochester, Rochester, NY, United States.
Front Cardiovasc Med. 2022 Jul 11;9:954780. doi: 10.3389/fcvm.2022.954780. eCollection 2022.
Recent advances have steadily increased the number of proteins and pathways known to be involved in the development of cerebral cavernous malformation (CCM). Our ability to synthesize this information into a cohesive and accurate signaling model is limited, however, by significant gaps in our knowledge of how the core CCM proteins, whose loss of function drives development of CCM, are regulated. Here, we review what is known about the regulation of the three core CCM proteins, the scaffolds KRIT1, CCM2, and CCM3, with an emphasis on binding interactions and subcellular location, which frequently control scaffolding protein function. We highlight recent work that challenges the current model of CCM complex signaling and provide recommendations for future studies needed to address the large number of outstanding questions.
最近的进展稳步增加了已知参与脑海绵状血管畸形（CCM）发展的蛋白质和信号通路的数量。然而，我们将这些信息整合为一个连贯且准确的信号模型的能力受到限制，因为我们对核心CCM蛋白（其功能丧失驱动CCM发展）如何被调控的认识存在重大差距。在这里，我们回顾了关于三种核心CCM蛋白（支架蛋白KRIT1、CCM2和CCM3）调控的已知信息，重点关注经常控制支架蛋白功能的结合相互作用和亚细胞定位。我们强调了最近挑战CCM复合信号当前模型的工作，并为解决大量悬而未决的问题所需的未来研究提供了建议。
