Slmap, the Sarcolemma Membrane Associated Protein, is a cardiac membrane protein of great significance. It plays a crucial role in cardiac excitation-contraction (E-C) coupling and the adrenergic response of the heart [1,3]. Additionally, it is involved in the Hippo signaling pathway as its negative regulator, forming Hippo-inactivating condensates [2].

In cardiomyocytes, all three Slmap isoforms (Slmap-1,-2, and-3) are expressed, and they are downregulated in human dilated ventricles. Knockdown of Slmap in cultured cardiomyocytes leads to a reduced spontaneous contractile rate, mimicking heart failure performance, while overexpression of Slmap-3 promotes cardiomyocyte response to adrenergic stimuli by increasing intracellular calcium [3]. In the context of diabetes, Slmap gene polymorphisms are associated with the susceptibility of diabetic retinopathy in the Qatari population, with the rs17058639 C>T polymorphism being an independent risk factor for the development and severity of diabetic retinopathy [4].

In summary, Slmap is essential for normal cardiac function, especially in E-C coupling and response to adrenergic stimuli. Studies on Slmap, including those using knockdown models in cardiomyocytes, have revealed its potential role in heart failure and diabetic retinopathy, providing insights into the molecular mechanisms underlying these diseases and potentially guiding future therapeutic strategies.

References:

1. Nader, Moni. 2019. The SLMAP/Striatin complex: An emerging regulator of normal and abnormal cardiac excitation-contraction coupling. In European journal of pharmacology, 858, 172491. doi:10.1016/j.ejphar.2019.172491. https://pubmed.ncbi.nlm.nih.gov/31233748/

2. Wang, Li, Choi, Kyungsuk, Su, Ting, Zheng, Yonggang, Pan, Duojia. 2022. Multiphase coalescence mediates Hippo pathway activation. In Cell, 185, 4376-4393.e18. doi:10.1016/j.cell.2022.09.036. https://pubmed.ncbi.nlm.nih.gov/36318920/

3. Nader, Moni, Alsolme, Ebtehal, Alotaibi, Shahd, Bakheet, Dana, Dzimiri, Nduna. 2019. SLMAP-3 is downregulated in human dilated ventricles and its overexpression promotes cardiomyocyte response to adrenergic stimuli by increasing intracellular calcium. In Canadian journal of physiology and pharmacology, 97, 623-630. doi:10.1139/cjpp-2018-0660. https://pubmed.ncbi.nlm.nih.gov/30856349/

4. Upadhyay, Rohit, Robay, Amal, Fakhro, Khalid, Crystal, Ronald G, Ding, Hong. 2015. Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population. In Journal of translational medicine, 13, 61. doi:10.1186/s12967-015-0411-6. https://pubmed.ncbi.nlm.nih.gov/25880194/