Spotlights
Myofibrillar Myopathies
Plectin deficiency in skeletal muscle leads to desmin IF network aggregation and loss of myofiber integrity. Using immortalized, differentiation-competent myoblast cell cultures established from plectin-KO mouse muscle for drug screening, we found a chemical chaperone (4-PBA) that alleviates protein aggregation and increases muscle strength in mice, setting the stage for clinical studies.
Epidermolysis bullosa simplex
Severe skin blistering is the hallmark of most plectinopathies. The analysis of knock-in mice mimicking a dominant human plectin mutation provided new insights into the function of isoform P1a and hemidesmosome-stabilizing mechanisms based on plectin oligomerization (see micrograph). In situ cleavage of P1a by proteases (calpain-1) was revealed as the likely pathomechanism of the disease EBS-Ogna.
Learning and memory
P1c is the major isoform of plectin expressed in neurons and glial cells. Mice specifically lacking P1c show learning and long-term memory deficits. We found that P1c (contrary to other variants) binds to microtubules favoring their dynamics by counteracting stabilization. Presently, we are investigating mechanistic links between plectin-mediated cytoskeleton rearrangements and memory formation.
Invadopodia and cancer cell invasiveness
Plectin together with its IF partner vimentin is strongly upregulated in several types of cancer, and is being developed as a tumor cell surface biomarker. In highly invasive cancer cells, formation of cellular protrusions (invadopodia) penetrating surrounding matrices is strictly plectin-dependent. We are interested in the mechanisms involving plectin-mediated exosome secretion and metastases.
12:30 - 13:30
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