Intermediate Filaments

Question 1

rules for filaments

Answer 1

must be dynamic, flexible, and strong

Question 2

intermediate filaments

Answer 2

coiled-coil proteins with no polarity; stronger and more flexible than MTs and actin

Question 3

vimentin

Answer 3

endothelial cell IFs

Question 4

keratin

Answer 4

epithelial cell IFs

Question 5

desmin

Answer 5

muscle IFs

Question 6

neurofilaments

Answer 6

nerve cell IFs

Question 7

IF structure

Answer 7

globular amino and carboxy terminals with a central alpha helical rod domain; coiled coil dimers

Question 8

transglutamination of IFs

Answer 8

toughens keratins in hair, skin, and nails

Question 9

phosphorylation of IFs

Answer 9

lamins are phosphorylated by a PK in prophase for disassembly before cell cycle

Question 10

dephosphorylation of IFs

Answer 10

lamins are dephosphorylated for reassembly in telophase

Question 11

keratin filament

Answer 11

need both type I and type II

Question 12

epidermolysis bullosa simplex

Answer 12

mutations in keratins at basal layer

Question 13

epidermolytic hyperkeratosis

Answer 13

mutations in keratins in spinous layer above basal layer

Question 14

EBS mutants

Answer 14

disrupt cytokeratin interactions with desmosomes and hemidesmosomes

Question 15

muscle IF diseases

Answer 15

mutations in desmin gene in muscles

Question 16

desminopathies

Answer 16

can be due to mutation in desmin gene or the desmin chaperone; wide range of clinical presentations; autosomal dominant

Question 17

nuclear lamin

Answer 17

make up structural meshwork under nuclear membrane

Question 18

A lamins

Answer 18

one gene LMNA makes two different proteins (A and C) by alternative splicing; expressed in late development

Question 19

B lamins

Answer 19

two related genes - LMNB1, LMNB2 that are expressed throughout development

Question 20

formation of lamin A vs. B

Answer 20

WT with CAAX box at carboxy end –> farnesylation –> C-terminal cleavage –> methylation –> lamin A is cleaved upstream while lamin B keeps the methylation

Question 21

laminopathies

Answer 21

defects in LMNA; muscular dystrophies, lipodystrophies, peripheral neuropathy syndromes, and progeria

Question 22

muscular dystrophies

Answer 22

lamins do not perform properly leading to misshapen nucleus; mutation in coiled coil domain (can develop late in life)

Question 23

lipodystrophies

Answer 23

defects are found in IG tail which causes target destruction –> altered gene expression

Question 24

progeria mutation

Answer 24

point mutation (C to T) changes a splice site near last exon, causing loss of around 50 amino acids

Question 25

How does new splice site cause progeria?

Answer 25

in processing of lamin A, upstream cleavage after methylation is prevented because of new splice site –> causes accumulation of progerin (prelamin a)