核膜的侵陷以不同的形状发生,尺寸,和构图。这些多形性内陷的一部分构成了核质网(NR),而其他人只是核褶皱。我们将NR定义为由内部和外部核膜组成的管状内陷,或者只有内核膜。具体来说,内部和外部核膜的内陷也称为II型NR,而仅内核膜的那些被定义为I型NR。NR的形成和结构由与核膜相关的蛋白质决定,这会引起高的膜曲率,导致管状内陷。在这里,我们回顾并讨论了核内陷的最新知识,特别是NR。核膜管状内陷的增加与几种病理有关,如层粘连病,癌症,(可逆性)心力衰竭,和老年痴呆症。此外,病毒可以诱导I型和II型NR。在层粘连病中,整个细胞核中的A型层合蛋白的量通常减少,或者层合蛋白或层合蛋白相关蛋白的组织受到干扰。此外,层粘连蛋白的过表达或层粘连蛋白法尼基化状态的调节会影响NR的形成,证实了层板加工在NR形成中的重要性。病毒感染通过层粘连蛋白的(去)磷酸化重组核层,导致核层的厚度不均匀,进而导致核膜的分叶和内部核膜的内陷的形成。由于大多数关于NR的研究都是用细胞培养物进行的,我们提供了这些结构在体内存在的额外证据,专注于各种分化的心血管和造血细胞。此外,我们通过薄片A/C和B1组织的超分辨率图像证实了对NR薄片组成的了解。最后,通过证明层蛋白的(过度)表达可以诱导异常的NR结构,我们进一步强调了层蛋白在NR形成中的重要作用。
Invaginations of the nuclear membrane occur in different shapes, sizes, and compositions. Part of these pleiomorphic invaginations make up the nucleoplasmic reticulum (NR), while others are merely nuclear folds. We define the NR as tubular invaginations consisting of either both the inner and outer nuclear membrane, or only the inner nuclear membrane. Specifically, invaginations of both the inner and outer nuclear membrane are also called type II NR, while those of only the inner nuclear membrane are defined as type I NR. The formation and structure of the NR is determined by proteins associated to the nuclear membrane, which induce a high membrane curvature leading to tubular invaginations. Here we review and discuss the current knowledge of nuclear invaginations and the NR in particular. An increase in tubular invaginations of the nuclear envelope is associated with several pathologies, such as laminopathies, cancer, (reversible) heart failure, and Alzheimer\'s disease. Furthermore, viruses can induce both type I and II NR. In laminopathies, the amount of A-type lamins throughout the nucleus is generally decreased or the organization of lamins or lamin-associated proteins is disturbed. Also, lamin overexpression or modulation of lamin farnesylation status impacts NR formation, confirming the importance of lamin processing in NR formation. Virus infections reorganize the nuclear lamina via (de)phosphorylation of lamins, leading to an uneven thickness of the nuclear lamina and in turn lobulation of the nuclear membrane and the formation of invaginations of the inner nuclear membrane. Since most studies on the NR have been performed with cell cultures, we present additional proof for the existence of these structures in vivo, focusing on a variety of differentiated cardiovascular and hematopoietic cells. Furthermore, we substantiate the knowledge of the lamin composition of the NR by super-resolution images of the lamin A/C and B1 organization. Finally, we further highlight the essential role of lamins in NR formation by demonstrating that (over)expression of lamins can induce aberrant NR structures.