Lecture 24 - Desmosomes

desmosomes

provide strong adhesions between epithelial and muscle cells

disc shaped (spot welds) between adjacent cells

function of desmosomes

confer mechanical strength to tissues

desmosome KO

blistering diseases

Giulio Bizzozero

identified desmosomes, platelets and blood cells in bone marrow

desmocollin and desmoglein

link plasma membranes together

desmosomal cadherins (ca dependant)

mammals have 5 dsc and 4 dsg

DSC and DSG structure

5 extra cellular loops

alternatively spliced

plakoglobin

gamma catenin

links dsc/dsg to desmoplakin, plakophilin and IF

bind to cadherin-specific domain of dsc/dsg

plakophilin

PKP1

binds to dsg, desmoplakin and IF

clusters proteins in desmosomes

ectodermal dysplasia

affects development of teeth, nails, sweat glands and hair

skin fragility syndrome

skin blistering

PKP2 null mice

embryologically lethal

cardiac defects (myocardium)

desmoplakin

most abundant desmosome protein

anchors plaque to IF

dsp 1 and 2

desmoplakin in the heart

joins cardiomyocytes together

desmoplakin KO

die at E6.5

hemidesmosomes

molecular difference to desmosomes

integrin based (not cahderin)

attach IF cytoskeleton to ECM

integrins

a6B4 integrin

used for hemidesmosome assembly and stability

integrins and keratin

less keratin = less hemidesmosomes = faster cell motility