Intermediate filaments in health and disease 1988 1999 2004 2007 2007 2008 1 2004 2007 2008 2000 2004 2006 2008 2007 2007 2008 1998 2006 2006 Table 1 Intermediate filament proteins Type Name/Localization Disease location Remarks n K9-28 (epithelia) K10,14,16,17-skin Acidic keratins K31-40 (hair/nail) K12-cornea (pI < 5.7) K13-stratified mucosa Type I/II obligate 1:1 polymers K16,17-nail  a  n K1-8, K71-80 (epithelia) K1,2e,5,9-skin Basic keratins K81-86 (hair/nail) K3-cornea (pI ≥ 6.0) K4-stratified mucosa Type I/II obligate 1:1 K6a,6b-nail polymers a  a  III Desmin (muscle) Muscle, heart Desmin, vimentin and GFAP are found in stellate cells Vimentin (mesenchymal)  Peripherin (neurons) a a GFAP (astrocytes/glia) Brain IV NF-L (neurons) a α-internexin forms polymers with NFs NF-M (neurons) a a  NF-H (neurons) a Synemin β is also called desmuslin. α-internexin (CNS neurons)  Nestin-stem cell marker Synemins (muscle)   Syncoilin (muscle)   Nestin   V Lamin A/C (ubiquitous) Heart, muscle, fat, premature aging, complex defects The only nuclear IFs, longer rod domain Lamin B1/2 (ubiquitous)  Orphan Phakinin (lens) Lens Beaded filaments in lens epithelia Filensin (lens) Lens  a 2006 2 2005 2006 2007 2005 2 2004 2007 2007 2005 2008 Table 2 Examples of IF-associated proteins Type of interaction Examples Function Anchoring Desmoplakin, BPAG1, α-dystobrevin Tissue architecture Cytolinker Plectin, Filaggrin, Cellular architecture Chaperones Hsp27, α-B-crystallin, Hsp70 Protein folding Kinases PKC, Cdk5 IF regulation, phosphate sink, cell cycle Adaptor proteins 14-3-3 protein, AP-3 Multiple effects Membrane proteins Polycystin-1 Unknown Apoptotic proteins TRADD, TNFR2, C-Flip, Caspase3/9 Apoptosis regulation Motor proteins Dynein, Kinesin Movement of IF components 2006 2007 2007 2007 2006 2007 2007 1999 2004 2004 2004 2008 1998 2004 2004 2004 2001 2002 2004 1975 1982 1994 2000 2007 Keratins as epithelially expressed IFs 2006 2007 2008 1 2006 1 2002 2006 2000 2004 1982 1999 2002 1982 1999 2002 2007 1982 2004 2002 1998 1998 1985 2002 2007 1982 1999 2004 2006a b 2007 2002 2007 1999 2006 2004 2006 2008 2008 2006 1998 2006 2004 Hepatic phenotype in keratin-deficient transgenic animals 3 2002 2002 2007 2004 2002 2004 2002 2004 3 2001 Table 3 IFs of liver cell populations Cell type IF composition Hepatocyte a Oval cells K7/K8/K18/K19 Cholangiocyte K7/K8/K18/K19 Kupffer cell Vimentin Stellate cell b Endothelial cell Vimentin 2002 a 1997 b 2001 2007 2002 2004 2007 2007 1995 1996 2008 2007 1998 2006 2002a 2003 2007 2001 2004 Keratin variants in liver disease 2001 2003a 2005 P 2006 2005 2007 2007 P P 2007 2004 2004 1998 2004 2004 2007 2002 2006 2007 2007 2002 2005 2007 2002b 2006 2004 2006 2005 2005 2001 2003 2002 2003 2007 2007 2008 1995 2001 2004 2007 2005 2006 2005 2003b 2008 2006 Keratin network alteration in steatohepatitis of the alcoholic (ASH) and the non-alcoholic (NASH) type 2004 2005 1911 2000 2007 1 2008 Fig. 1 a blue structures red center b green red channel c d red channel c green channel d  2004 2007 2004 2007 2 1994 2007 2007 1987 Fig. 2 a b c d  This suggests that MDBs require either a specific pathogenetic constellation or genetic predisposition for its formation, which is present only in a subset of patients. 1988 2004 1999 2006 2007 2003 1987 1999 2004 2005 Morphology and composition of MDBs 1911 2000 2007 2007 1972 1972 2000 2002 2003 2007 2007 1 2 1990 1992 1991 1993 1986 1992 1995 2000 1 Pathogenesis of MDBs 1975 1982 2000 2004 2007 3 Fig. 3 green red d b a c blue pigment d  2004 2007 1994 2000 3 2000 2004 2007 2000 2004 2007 2007 4 2004 1. Enhanced oxidative stress 2. Disproportional K8/K18 expression together with keratin modifications 3. Chaperone dysfunction 4. Elevated p62 levels 5. Insufficient protein degradation 1981 2002 2006 2006 1991 1993 2008 1981 1980 2008 2005 Fig. 4 red stretches  1985 1989 2004 2003 2007 2008 2007 2007 2000 1998 2005 2000 2007 2002 2007 1992 2000 2002b 2007 2006 2000 1992 2007 2007 1991 1993 2004 2005 2006 Strnad et al. submitted 2005 1998 2001 2002 2007 1996 2005 2004 2008 2003 2005 2007 2007 2008 2005 2008 2007 2007 2002 2006 2002 2006 2005 2003 2002 2002 2001 2008 2001 2002 2002 1998 1999 2004 2007 2007 Pathologic significance of MDBs 2004 2006 1997 1999 2001 2001 2004 2004 2007 2000