MACF1
Description
The MACF1 (microtubule actin crosslinking factor 1) is a protein-coding gene located on chromosome 1.
MACF1 (Microtubule-actin cross-linking factor 1) is a protein encoded by the MACF1 gene in humans. It is a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains, acting as a bridge between different cytoskeletal elements. MACF1 facilitates actin-microtubule interactions at the cell periphery and links the microtubule network to cellular junctions. It belongs to the spectraplakin family of +TIPs (proteins that bind to growing microtubule ends). MACF1 is known by various names, including ACF7, MACF, macrophin, trabeculin α, and ABP620. Different isoforms of MACF1 are generated through alternative splicing, and it is crucial for cell migration in processes like wound healing. MACF1 is an enormous protein consisting of 5380 amino acid residues.
Isoform 2 of MACF1 is an F-actin-binding protein that links actin to other cytoskeletal elements and also binds to microtubules. It plays a crucial role in stabilizing microtubules at the cell cortex, particularly in the context of ERBB2 signaling. Additionally, it acts as a positive regulator of the Wnt receptor signaling pathway, facilitating the movement of the AXIN1 complex (comprising APC, CTNNB1, and GSK3B) from the cytoplasm to the cell membrane. MACF1 isoform 2 exhibits actin-regulated ATPase activity, which is essential for controlling the assembly and dynamics of focal adhesions. Its interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules anchors microtubule minus ends to actin filaments, impacting focal adhesion size and cell migration. This isoform might also contribute to the delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4. MACF1 isoform 2 plays a key role in wound healing and epidermal cell migration, particularly in the upward migration of bulge cells in response to wounding. This function is attributed to its ability to coordinate microtubule dynamics and polarize hair follicle stem cells. As a regulator of actin and microtubule arrangement and stabilization, MACF1 isoform 2 is essential for neurite outgrowth, branching, and spine formation during brain development.
MACF1 is also known as ABP620, ACF7, KIAA0754, LIS9, Lnc-PMIF, MACF, OFC4.
Associated Diseases
- Posterior-predominant lissencephaly-broad flat pons and medulla-midline crossing defects syndrome
- Lissencephaly 9 with complex brainstem malformation
