Microfilaments

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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