title: Actin depolymerisation and crosslinking join forces with myosin II to contract actin coats on fused secretory vesicles.
abstract: In many secretory cells actin and myosin are specifically recruited to the surface of secretory granules following their fusion with the plasma membrane. Actomyosin-dependent compression of fused granules is essential to promote active extrusion of cargo. However, little is known about molecular mechanisms regulating actin coat formation and contraction. Here, we provide a detailed kinetic analysis of the molecules regulating actin coat contraction on fused lamellar bodies in primary alveolar type II cells. We demonstrate that ROCK1 and myosin light chain kinase 1 (MLCK1, also known as MYLK) translocate to fused lamellar bodies and activate myosin II on actin coats. However, myosin II activity is not sufficient for efficient actin coat contraction. In addition, cofilin-1 and α-actinin translocate to actin coats. ROCK1-dependent regulated actin depolymerisation by cofilin-1 in cooperation with actin crosslinking by α-actinin is essential for complete coat contraction. In summary, our data suggest a complementary role for regulated actin depolymerisation and crosslinking, and myosin II activity, to contract actin coats and drive secretion.
authors: Department of General Physiology, University of Ulm, Albert-Einstein Allee 11, 89081 Ulm, Germany.
authors: Pika
authors: P
authors: Miklavc
authors: Department of General Physiology, University of Ulm, Albert-Einstein Allee 11, 89081 Ulm, Germany.
authors: Konstantin
authors: K
authors: Ehinger
authors: Department of General Physiology, University of Ulm, Albert-Einstein Allee 11, 89081 Ulm, Germany.
authors: Ayesha
authors: A
authors: Sultan
authors: Department of General Physiology, University of Ulm, Albert-Einstein Allee 11, 89081 Ulm, Germany.
authors: Tatiana
authors: T
authors: Felder
authors: Institute for Experimental Physics, University of Ulm, Albert-Einstein Allee 11, 89081 Ulm, Germany.
authors: Patrick
authors: P
authors: Paul
authors: Institute for Experimental Physics, University of Ulm, Albert-Einstein Allee 11, 89081 Ulm, Germany.
authors: Kay-Eberhard
authors: KE
authors: Gottschalk
authors: Department of General Physiology, University of Ulm, Albert-Einstein Allee 11, 89081 Ulm, Germany manfred.frick@uni-ulm.de.
authors: Manfred
authors: M
authors: Frick
mesh_terms: D008841:Actin Cytoskeleton; D000185:Actinin / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology; D005455:Fluorescent Antibody Technique; D008561:Membrane Fusion / Q000502:physiology*; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022142:Secretory Vesicles / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D012333:RNA, Messenger; D000185:Actinin; C578418:ROCK1 protein, rat; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D024462:Myosin Type II; D020741:rho GTP-Binding Proteins
keywords: Cofilin; Lamellar body; MLCK; ROCK; Secretion; Surfactant
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