A028 Analysis of PDLIM proteins levels in HD models

<h3>Background</h3> Huntington’s disease is adult-onset neurodegeneration, but mutated huntingtin also causes premature differentiation of neural progenitors in brain development. Seven members of mammalian PDLIM protein family interact with many partners, mainly actin cytoskeleton proteins, and regulate diverse cellular functions, including neurite growth and synapse formation. <h3>Aims</h3> To identify changes in the protein levels of PDLIM protein family members in human control and HD NSC and in zQ175 knock-in HD mouse model. <h3>Methods/Techniques</h3> Using data independent acquisition LC-MS/MS proteomics, we analyzed whole cell lysates from control and HD iPS cell derived NSCs. Using western blot, we have analyzed PDLIM1, 5 &amp; 7 expression in zQ175 HD mouse derived E13.5 NSCs and in adult zQ175 mouse striatal synaptosomes, cytoplasmic and nuclear fraction. <h3>Results/Outcome</h3> Using LC-MS/MS proteomics, we have identified significant increase in PDLIM5 levels in human HD NSCs compared to controls. Additionally, four of the other PDLIMS, namely PDLIM1, PDLIM2, PDLIM4 and PDLIM7 (Figure 1) were also increased in HD cells. PDLIM3 and PDLIM6 were not detected in any of the samples. PDLIM5 levels were not changed between WT and zQ175 striatal synaptosomes but were decreased in zQ175 striatal nuclear fraction compared to WT mice. PDLIM1, 5 &amp; 7 expression was confirmed in mouse E13.5 derived WT and zQ175 NSCs. <h3>Conclusions</h3> PDLIM5 is implicated in regulation of actin cytoskeleton and dendritic spine morphology. Detected increase in PDLIM5 levels in HD NSCs could play a role in developmental changes caused by mHTT. This work was supported by the Czech Science Foundation project 22-24983S.