A: Sucrose density fractionation of postnuclear supernatant in the
presence of non-ionic detergent (1% TX-100) revealed weak DYRK1A
immunoreactivity in detergent-soluble fractions 1 and 2 (containing cytosol
proteins) and a strong immunoreactivity in β-actin–rich and
detergent-resistant fractions 11 and 12 (cytoskeletal proteins). Fractions
3–5 enriched in membrane lipid rafts (shown by the presence of
integrin-α2) did not contain DYRK1A. Equal vols of 20 μL of each
fraction were loaded per lane. B. To estimate the size of DYRK1A,
100,000 × g supernatant (cytosol) and 100,000 × g pellet
(cytoskeleton fraction) were subjected to gel filtration on Superose 6.
Cytosolic DYRK1A that peaked in fractions 18–20 comprised proteins in
the range of 232–158 kDa (upper panel). DYRK1A from the
detergent-resistant cytoskeletal fraction (lower panel), solubilized in 8 M urea
and subjected to gel filtration on Superose 6, peaked in fraction 6 and
comprised protein complexes larger than 2,000 kDa and cytoskeletal proteins:
neurofilament heavy (nf-200) and medium (nf-160), α-tubulin, and
β-actin. Images of mAb 8D9–detected Western blots are shown with
the position of molecular weight markers of 2,000, 669, 440, 232, 158, 44, and
25 kDa. C: Western blots of DYRK1A immunoprecipitates revealed
several cytoskeletal proteins co-precipitated with DYRK1A. The material
immunoprecipitated with pAb R420 was divided in five equal parts to detect
DYRK1A (mAb 8D9), β-actin, α-tubulin, heavy neurofilament, and
tau proteins in WB. Non-immune rabbit IgG—a specificity control of
IP—is shown in lane (−), lane In marks 10% of the
reaction input.