Table 1 Intermediate Wlament proteins 736 Type I (n = 28) II (n = 26) III IV V Orphan Name/Localization K9-28 (epithelia) K31-40 (hair/nail) K1-8, K71-80 (epithelia) K81-86 (hair/nail) Desmin (muscle) Vimentin (mesenchymal) Peripherin (neurons) GFAP (astrocytes/glia) NF-L (neurons) NF-M (neurons) NF-H (neurons) -internexin (CNS neurons) Synemins (muscle) Syncoilin (muscle) Nestin Lamin A/C (ubiquitous) Lamin B1/2 (ubiquitous) Phakinin (lens) Filensin (lens) Disease location K10,14,16,17-skin K12-cornea K13-stratiWed mucosa K16,17-nail K18a-liver K1,2e,5,9-skin K3-cornea K4-stratiWed mucosa K6a,6b-nail K8a-liver K75a,81,83,85,86-hair Muscle, heart Braina, spinal corda Brain Braina, spinal cord Braina, spinal corda Brain, spinal corda Heart, muscle, fat, premature aging, complex defects Lens Lens Histochem Cell Biol (2008) 129:735–749 Remarks Acidic keratins (pI < 5.7) Type I/II obligate 1:1 polymers Basic keratins (pI ¸ 6.0) Type I/II obligate 1:1 polymers Desmin, vimentin and GFAP are found in stellate cells -internexin forms polymers with NFs Synemin is also called desmuslin. Nestin-stem cell marker The only nuclear IFs, longer rod domain Beaded Wlaments in lens epithelia a Not a causative association, variants represent a risk factor. For an overview about the new keratin nomenclature, see Schweizer et al. (2006) contribute to the structural heterogeneity and are major sites of posttranslational modiWcations with phosphoryla- tion being the best characterized one (Omary et al. 1998; 2006). This makes them important regulatory domains, since dynamic changes in phosphorylation status are responsible for alterations in IF dynamics, solubility, and organization (Omary et al. 2006). In addition to the posttranslational modiWcation, IF func- tion is modiWed and complemented through interaction with a variety of IF-associated proteins (IFAP; Table 2; Green et al. 2005; Omary et al. 2006; Kim and Coulombe 2007). These proteins can be subdivided into several sub- groups, which reXect multiple IF functions (Green et al. 2005). For example, IFs interact with a variety of anchoring proteins thereby forming transcellular networks which contribute to proper tissue architecture. IFAPs also include several cytolinker proteins, which provide the structural framework for coordinated cytoskeletal function (Table 2). By doing that, they are important mechanical stabilizers 123 and accordingly, IF disruption results in increased mechani- cal fragility (Omary et al. 2004; Ku et al. 2007; Herrmann et al. 2007). The scaVolding function of IFs is best seen in IF-deWcient animals, who exhibit disrupted cellular archi- tecture, protein mistargeting as well as alterations in orga- nelle localization and function (Toivola et al. 2005). In the case of lamin deWciencies, the impairment of nuclear com- position has profound impact on many aspects of normal nuclear functions such as epigenetic changes, chromatin organization or DNA transcription, and repair (Dechat et al. 2008). IFs are not just simple cellular scaVolds, they rather build complex signaling platforms (Pallari and Eriksson 2006; Kim and Coulombe 2007). IFs interact with a variety of enzymatic and adaptor proteins, thereby aVecting a multi- tude of cellular functions. For example, keratins associate with 14-3-3 proteins in a phosphorylation-dependent man- ner and this interaction regulates cell growth and cell cycle progression (Ku et al. 2007; Kim and Coulombe 2007). IF