Alternative splicing occurs in over 95% of protein-coding genes and contributes to the diversity of the human proteome. Apolipoprotein E receptor 2 (apoER2) is a critical modulator of neuronal development and synaptic plasticity in the brain and is enriched in cassette exon splicing events, in which functional exons are excluded from the final transcript. These alternative splicing events affect apoER2 function, as individual apoER2 exons tend to encode distinct protein functional domains. Although several apoER2 splice variants have been characterized, much work remains to understand how apoER2 splicing events modulate distinct apoER2 activities, including ligand binding specificity, synapse formation and plasticity. Additionally, little is known about how apoER2 splicing events are regulated. Often, alternative splicing events are regulated through the combinatorial action of RNA-binding proteins and other epigenetic mechanisms, however, the regulatory pathways corresponding to each specific exon are unknown in most cases. In this mini-review, we describe the structure of apoER2, highlight the unique functions of known isoforms, discuss what is currently known about the regulation of apoER2 splicing by RNA-binding proteins and pose new questions that will further our understanding of apoER2 splicing complexity.

超过95％的蛋白质编码基因中都存在其他剪接，并有助于人类蛋白质组的多样性。载脂蛋白E受体2（apoER2）是大脑中神经元发育和突触可塑性的关键调节剂，富含盒式外显子剪接事件，其中功能性外显子从最终转录本中排除。这些替代的剪接事件影响apoER2的功能，因为单个apoER2外显子倾向于编码不同的蛋白质功能域。尽管已鉴定了几种apoER2剪接变体，但仍有许多工作要了解apoER2剪接事件如何调节独特的apoER2活性，包括配体结合特异性，突触形成和可塑性。另外，对于如何调控apoER2剪接事件知之甚少。经常，可变的剪接事件是通过RNA结合蛋白和其他表观遗传机制的组合作用来调节的，但是，在大多数情况下，与每个特定外显子相对应的调节途径是未知的。在本微型综述中，我们描述了apoER2的结构，突出了已知同工型的独特功能，讨论了当前有关RNA结合蛋白对apoER2剪接调控的知识，并提出了新的问题，这些将进一步加深我们对apoER2剪接复杂性的理解。