Nuclear envelope: positioning nuclei and organizing synapses

Abstract

The nuclear envelope plays an essential role in nuclear positioning within cells and tissues. This review highlights advances in understanding the mechanisms of nuclear positioning during skeletal muscle and central nervous system development. New findings, particularly about A-type lamins and Nesprin1, may link nuclear envelope integrity to synaptic integrity. Thus synaptic defects, rather than nuclear mispositioning, may underlie human pathologies associated with mutations of nuclear envelope proteins.

Figure 1

Topological representation and domain composition of Nesprins 1, 2, 3 and 4, which are encoded by distinct genes, in the context of their interaction with SUN proteins and cytoskeletal components. Dashed arrows indicate direct SUN/KASH interactions. INM, inner nuclear membrane. ONM, outer nuclear membrane.

Figure 2

Nuclear movements accompanying CNS development. (A) Depiction of interkinetic nuclear migration within neural precursor cells (blue nuclei). (B) Centrosome-mediated nuclear translocation within post-mitotic neurons (green nuclei) migrating towards their final laminar position. NBL, neuroblast layer. (C) Apical migration of cone photoreceptor nuclei during postnatal retinogenesis. OS, outer segment (phototransduction). IS, inner segment (ER, mitochondria). ONL, outer nuclear layer that contains photoreceptor nuclei. P, postnatal day. The boxed inset shows the displacement of endogenous Nesprins from NE to ER membranes upon transgenic expression of EGFP-KASH2 specifically targeted to differentiating cone photoreceptors.

Figure 3

Role of NE components in skeletal muscle development. (Box I) Depiction of LINC complexes in the context of myonucleus anchorage at the neuromuscular junction. AchRs, Acetylcholine Receptors. NPC, nuclear pore complex. (Box II) A-type lamins form nuclear foci at sites where DFz2C and ribonucleoparticles (RNPs) are trafficked across the NE. (Box III) Depiction of local translation of MSP-300 (Nesprin1) and other mRNAs at the NMJ.