Lasp-1 regulates podosome function

• Published in: PloS one 2012-04, Vol.7 (4), p.e35340-e35340
• Main Authors: Stölting, Miriam, Wiesner, Christiane, van Vliet, Vanessa, Butt, Elke, Pavenstädt, Hermann, Linder, Stefan, Kremerskothen, Joachim
• Format: Article
• Language: English
• Subjects: Actin; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Biology; Cell adhesion; Cell adhesion & migration; Cell Line; Cell migration; Cells, Cultured; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Cytoskeleton; Cytoskeleton - metabolism; Cytosol; Degradation; Dopamine; Extracellular matrix; Focal Adhesions - metabolism; Humans; Hygiene; Immunofluorescence; Immunoglobulins; Kinases; Lamellipodia; LIM Domain Proteins - genetics; LIM Domain Proteins - metabolism; Localization; Macrophages; Macrophages - metabolism; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Molecular structure; Motility; Muscle proteins; Myosin; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Pancreatic cancer; Phosphorylation; Protein binding; Proteins; Pseudopodia; Pseudopodia - metabolism; Rats; RNA, Small Interfering - genetics; Rodents; Signaling; siRNA; Smooth muscle; Vinculin; Vinculin - metabolism; Zyxin - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035340

Eukaryotic cells form a variety of adhesive structures to connect with their environment and to regulate cell motility. In contrast to classical focal adhesions, podosomes, highly dynamic structures of different cell types, are actively engaged in matrix remodelling and degradation. Podosomes are composed of an actin-rich core region surrounded by a ring-like structure containing signalling molecules, motor proteins as well as cytoskeleton-associated proteins. Lasp-1 is a ubiquitously expressed, actin-binding protein that is known to regulate cytoskeleton architecture and cell migration. This multidomain protein is predominantely present at focal adhesions, however, a second pool of Lasp-1 molecules is also found at lamellipodia and vesicle-like microdomains in the cytosol.In this report, we show that Lasp-1 is a novel component and regulator of podosomes. Immunofluorescence studies reveal a localization of Lasp-1 in the podosome ring structure, where it colocalizes with zyxin and vinculin. Life cell imaging experiments demonstrate that Lasp-1 is recruited in early steps of podosome assembly. A siRNA-mediated Lasp-1 knockdown in human macrophages affects podosome dynamics as well as their matrix degradation capacity. In summary, our data indicate that Lasp-1 is a novel component of podosomes and is involved in the regulation of podosomal function.