Figure 3. IF protein sumoylation regulates filament organization and solubility properties.

a. Sumoylation regulates the organization of IFs. Sumoylation is important for the proper filament organization of IFB-1, a C. elegans cytoplasmic IF that forms epidermal attachment structures¹². In SUMO-null worms IFB-1 filaments appear as a heterogeneous population of different size aggregates, long filaments and ring-like structures, and the occurrence of large aggregates increases with age. ¹² Similarly, sumoylation of human lamin A in the highly-conserved rod domain at Lys-201 is important for its proper nuclear localization¹⁴. The sumoylation deficient lamin A K201R forms abnormal puncta inside the nuclei or at the nuclear periphery¹⁴. Laminopathy-associated lamin A mutants, as exemplified by those listed in the figure, are hyposumoylated and exhibit abnormal organization in comparison to normal lamin A^14,96. b. Sumoylation regulates the solubility of IFs. Sumoylation sequesters a fraction of IFB-1 into a soluble cytoplasmic pool and facilitates the exchange between the soluble and polymerized IFB-1 pool¹². Sumoylation of wild-type polymerized human K8 and K18 (depicted by the yellow filaments in the middle) is not readily detectable under basal but is highly upregulated upon the re-organization of these IFs in response to apoptosis, stress, disease, or in the context of K8 variants that predispose to liver disease¹³. Monosumoylation promotes K8 solubility in vitro, similar to IFB-1, whereas pathologic hypersumoylation is associated with diminished K8 solubility and formation of high molecular mass complexes¹³.