MACF1

Official Full Name

microtubule actin crosslinking factor 1

Organism

Homo sapiens

GeneID

23499

Background

This gene encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. The encoded protein is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Alternative splicing results in multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, May 2013]

Synonyms

ACF7; LIS9; MACF; OFC4; ABP620; KIAA0754; Lnc-PMIF;

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Detailed Information

Microtubule actin cross-linking factor 1 (MACF1) is a cytoskeletal protein that is ubiquitously expressed in mammalian cells and can cross-link with microtubules and crosslink with microfilaments. MACF1 is a very important cell junction factor that binds to microfilaments and microtubule cytoskeletal components and plays an important role in coordinating cell development and maintaining tissue integrity. MACF1 is a multi-domain cytoskeletal cross-linked protein with a relative molecular mass of 680 000, composed of 4433 amino acids. It is discontinuously distributed on the microfilaments and microtubule skeletons around the cells, and has the structural features of reticulin and dystrophin.

MACF1 Function

MACF1 may crosslink the microtubule skeleton and the microfilament skeleton by adjusting the assembly of the microtubule skeleton. MACF1 is the first protein to be widely expressed in mammalian cells and capable of binding to microfilaments and microtubule backbone networks. MACF1 also selectively limits the interaction between microfilaments and microtubules. Studies have shown that MACF1 interacts with microtubules and colocalizes with the microtubule backbone in the cytoplasm. MACF1 is a cytoskeletal cross-linking protein that binds to microtubules and microfilaments and is an integrator of microtubule-microfilament kinetics. The interaction between microfilaments and microtubules must be regulated by MACF1. MACF1 can participate in the directional movement of cells by regulating the polar growth of microfilaments and microtubules, and further participate in regulating various physiological functions of cells.

Figure 1. MACF1 structure and role in the Wnt/β-catenin signaling (Moffat, et al. 2017)

MACF1 Participates in Signal Transduction

Studies using mice that knocked out the MACF1 gene revealed that MACF1 is involved in the Wnt signaling pathway and acts as a regulatory factor responsible for the translocation of Axin and its related complexes from the cytosol to the cell membrane. Downregulation of MACF1 in cultured cells results in a decrease in Wnt-induced TCF/b-catenin transcriptional activation. In cultured fibroblasts, microtubules recombine to respond to activation of signaling pathways. It has been shown that the Rho effector molecule mDia is very important in stabilizing the orientation of microtubules. However, the mDia constitutive activation form does not promote microtubule stability when MACF1 is absent, suggesting that MACF1 may be an effector molecule downstream of mDia.

MACF1 and Development

The study found that MACF1 is highly expressed in the embryonic foregut and pleats of the 8.5 days (E8.5) of the nervous tissue, embryo development, and the primitive streak at 7.5 days of the embryo. MACF1-/- mice died during the gastrulation stage and showed diapause at 7.5 days of embryos, accompanied by defects in the primitive streak, protoplast and mesodermal. Studies have shown that the developmental expression profile of mouse ACF7 gene is studied by in situ hybridization experiments. The results show that ACF7 transcripts in 8.5-day mouse embryos are mainly in the dermatomes and nerve folds. In the late developmental stage, ACF7 is mainly expressed in neuromuscular tissues, and expression is significantly up-regulated in type II vesicle cells of the lungs before birth. Therefore, ACF7 plays a very important role in the development of nerves, muscles and lungs.

MACF1 and Disease

The disease caused by the mutation of MACF1 has not been reported yet. Elimination of the MACF1 gene may result in early embryonic death. The role of MACF1 in signal transduction suggests that MACF1 may be involved in tumorigenesis. Recently, in the breast cancer and colon cancer screening, 12% of breast cancer tumors have a mutation in MACF1, although the role of MACF1 in tumors has not been confirmed. In addition, MACF1 has been shown to be part of the Disc1 gene interactor, interacting with both the Disc1 gene and the dysbindin gene.

References:

Moffat, J. J. , Ka, M. , Jung, E. M. , Smith, A. L. , & Kim, W. Y. . (2017). The role of macf1 in nervous system development and maintenance. Seminars in Cell & Developmental Biology, S1084952116303184.
Maysimera, H. L. , Gumerson, J. D. , Gao, C. , Campos, M. , Cologna, S. M. , & Beyer, T. , et al. (2016). Loss of macf1 abolishes ciliogenesis and disrupts apicobasal polarity establishment in the retina. Cell Reports, 17(5), 1399-1413.
Hu L , Xiao Y , Xiong Z , et al. MACF1, versatility in tissue-specific function and in human disease[J]. Seminars in Cell & Developmental Biology, 2017:S1084952116303214.

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