Filamin

Filamine ( FLN) are proteins in eukaryotes and belong to the actin -binding proteins (ABP). They are involved in cross-linking of actin, a major component of the cytoskeleton, and the cross-linking of actin filaments with proteins in the cell membrane. Indirectly, they also play an important role in cell-cell and cell-matrix connections, the locomotion of cells ( cell motility ) and in the development of eukaryotes ( ontogeny ). Mutations in the coding filamin -B or -C genes can cause rare genetic diseases.

Nomenclature

The nomenclature was relatively patchy long time. Very many different names or abbreviations may easily lead to confusion. Only in the year 2001, a uniform nomenclature has been introduced. The acronym FLN a prefix is always preceded by the indicating from which organism the corresponding filamin was isolated:

• Hs for Homo sapiens (Human)
• Gg for Gallus gallus ( Bankivahuhn )
• Dm melanogaster Drosophila ( fruit fly Schwarzbäuchige )
• Dd for Dictyostelium discoideum ( type from the class of slime molds )

An overview of the various Filamine offers the following table:

The Filamine of man

Construction

In humans, there are 3 different Filamine: Filamin A ( α - filamin ), Filamin B ( β - filamin ) and filamin C ( γ - filamin ). They consist of 24 repetitions, each formed of about 96 amino acids. The carboxy-terminal (C -terminal ) end of the Filamine have a flexible hinge region, which is located in electron micrographs, V or Y -shaped. They provide the cross Verne lines a certain flexibility. Filaminen the A and B there are in each case for a further 2 isoforms, one with or without a second joint region.

Functions

The functions of the Filamine are numerous and are compounds, mainly mediates between actin and membrane proteins. There are now more than 20 of these interactions known. The membrane proteins are frequently to receptors in the cell relayed upon binding their ligand signals (so-called signal transduction ). The compounds of the Filamine be solved via signals or newly formed and can thus lead to a reorganization of the cytoskeleton. The signal transmission is mediated inter alia by phosphorylation and dephosphorylation.

An example is the interaction of A and B Filamine between actin and a receptor, which occurs, inter alia, in the blood platelets ( thrombocytes), the so-called von- Willebrand factor receptor. It plays an important role in the initiation of blood coagulation. The receptor binds its ligand, the von Willebrand factor, it is, inter alia, by the connection to an activation of the platelets and to a reorganization of the cytoskeleton. Another receptor, which plays a role in blood clotting and interacts with filamin, is the receptor for Tissue Factor.

Furthermore, can be solved through the interaction with several integrins cell-cell and cell-matrix connections or formed. Integrins bind, for example outside the cell structures of the connective tissue, such as collagen and filamin. They contribute to the stability of cell groups.

Filamin C has a specific amino acid sequence which interacts with the Z-line of the actin filaments in muscle cells. This leads to a cross-linking of muscle fibers and thus contributes to stabilization.

Medical importance

Mutations in the genes that code for the Filamine, can lead to many, but overall rare diseases.

Mutations in the C- filamin gene ( FLNC ) include the reason for the Filaminopathie, one form of the myofibrillar myopathy (MFM). MFM are a clinically and genetically heterogeneous group of muscle disorders which are characterized by focal resolution of muscle fibers as well as by the abnormal accumulation and aggregation of various proteins in the muscle fibers of patients. All previously described FLNC mutations affecting the dimerization domain. For p.W2710X mutation that leads to a deletion of the carboxy-terminal 16 amino acids in domain 24, it could be shown that in this way the dimerization is disrupted and the mutant Filaminmoleküle agglomerate and instead form aggregates. Furthermore, the mutant filamin C less stable and more susceptible to proteolysis. Clinically, the Filaminopathie leads to a slowly progressive muscle weakness that favors the stem near muscles concerns. A frequent and serious complication is respiratory insufficiency due to the involvement of the respiratory muscles dar.