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Microfilaments in fibroblasts of the mouse, fluorescence microscopy shown

Microfilaments are thread-like protein structures in eukaryotic cells. Together with the microtubules and intermediate filaments , they form the main mass of the cytoskeleton . They mainly consist of the protein actin and are therefore also known as actin filaments . The term “microfilament” comes from the fact that, with a diameter of only six nanometers, they are significantly thinner than the microtubules and intermediate filaments. Functionally, they play a role in active cell movements, in intracellular transport processes and in the mechanical stabilization of cells.

Assembling the filaments

Actin filaments, colors represent different layers.

G-actin (globular actin, a monomer) binds the nucleotide ATP . This monomer (ATP-actin) can now combine with other actin molecules - polymerize , whereby ATP-actin becomes ADP -actin with cleavage ( hydrolysis ) of an inorganic phosphate residue . The resulting chain of actin monomers thus forms the filamentous form of actin filaments , also called F-actin . The filament consists of two chains of polymerized G-actin monomers that wrap around each other like a helix. This actin-typical helix turn can be found regularly after 7 G-actins, which is why it is also called "actin helix" in order to protect it e.g. B. from the DNA double helix in their shape. Their diameter is 7 nm. Both forms of actin are in equilibrium in the cell, with monomers mainly in complex with actin-binding proteins, such as. B. Profilin occur.

Actin filaments have a polarity and have a rapidly polymerizing so-called (+) end and a slowly polymerizing (-) end. ATP actin binds preferentially at the (+) - end and the filament grows at this end. The ATP is then hydrolyzed to ADP , which reduces the strength of the bond with the neighboring actins. At the (-) - end, the hydrolysis of ATP to ADP is faster than the accumulation of a new ATP-actin, so that ADP-actin dissociates and the filament is shortened from this side. Actin monomers, however, bind ATP more strongly than ADP, thereby exchanging the nucleotide and can be reinserted at the (+) end. This rapid cycle is important for cell movements and is known as treadmilling .

Numerous accompanying proteins control the polymerization and degradation processes. In the muscle, for example, the filaments are stabilized by tropomyosin , which attaches to a filament along its entire length. Caldesmon is produced in cells outside the heart and skeletal muscles .

Certain proteins also cover the ends of the actin filaments and hinder or promote elongation or further breakdown. Other proteins prevent or promote the polymerization of G-actin or cause the breakdown of F-actin.

For example, the proteins cofilin and ADF (actin depolymerizing factor) attach to the (-) end and promote the dissociation of actin. The protein profilin, on the other hand, promotes incorporation at the (+) end. The binding of both cofilin and profilin is determined by the actin-bound nucleotide (ADP or ATP).

Also, post-translational modifications of actin are involved in the polymerization. So every fifth Aktinmonomer is in fibroblasts with a arginylation provided, which has a direct impact on the increased stability of actin filaments. Primarily beta-actin is modified.

The build-up and breakdown of actin filaments can be inhibited by cytoskeleton inhibitors . A bacterial homolog of actin is FtsA .

Immunofluorescence staining of the actin cytoskeleton (green) and the focal adhesion protein vinculin (red) in a fibroblast cell. The adhesion sites can be seen as red spots at the ends of the actin bundles.

Adapter and connection proteins

A large group of accompanying proteins , also known as actin-binding proteins (ABP), link actin filaments with one another and with other proteins. Fimbrin , Villin (internal structure of the microvilli), Filamin and Espin form cross connections and thus mechanically rigid bundles. α-actinin also forms bundles that are typically braced with myosin (see below). The filamine, in turn, forms three-dimensional networks (gels), such as those found under the plasma membrane.

Actin filaments radiate into several cell contacts , the adherence contacts and the focal contacts , but also into zonulae occludentes. They are anchored to the protein structures of the contacts via adapter proteins. Responsible for this are again α- actinin , vinculin and talin . The proteins of the family around Ezrin, Radixin , Moesin (ERM proteins) mediate short-term and dynamic bonds to the plasma membrane, for example when the cell shape changes and cell movement is active.

Certain protein groups create a mechanically stable connection between the dense actin network underlying the plasma membrane and the membrane. These proteins, which are also clinically important because of various hereditary diseases, are the dystrophins ( e.g. in muscle tissue , in the case of mutations in the dystrophin complex, muscular dystrophies ) and the spectrins ( e.g. responsible for the shape of the erythrocytes , e.g. in the case of defects, e.g. spherical cell anemia ). They are long, thinner proteins that perform their tasks in complexes with numerous other proteins.

Individual evidence

  1. KC Holmes, D. Popp, W. Gebhard, W. Kabsch: Atomic model of the actin filament. In: Nature . 347, 1990, pp. 21-22. PMID 2395461
  2. ^ TD Pollard, WD Earnshaw: Cell Biology . 1st edition. Saunders, 2004, ISBN 1-4160-2388-7 .
  3. D. Didry, MF Carlier, D. Pantaloni: Synergy between actin depolymerizing factor / cofilin and profilin in increasing actin filament turnover. In: J Biol Chem . 273 (40), 1998, pp. 25602-25611. PMID 9748225
  4. M. Karakozova, M. Kozak, CC Wong, AO Bailey, JR Yates, A. Mogilner, H. Zebroski, A. Kashina: Arginylation of beta-actin regulates actin cytoskeleton and cell motility. In: Science . 313 (5784), 2006, pp. 192-196. PMID 16794040