MACF1, versatility in tissue-specific function and in human disease
Section snippets
MACF1: a versatile spectraplakin
Microtubule actin crosslinking factor 1 (MACF1), also known as actin crosslinking factor 7 (ACF7), MACF, macrophin [1], and trabeculin-α [2], was firstly identified by screening for additional members of the actin crosslinker superfamily [3]. MACF1 is encoded by the MACF1 gene that is located on the human chromosome 1p32 and the mouse chromosome 4 [4], [5]. Gong and colleagues have identified that the human MACF1 gene comprises at least 102 exons and spans over 270 kb [4]. The MACF1 gene is a
MACF1’s functions in specific tissue
The ubiquitous expression pattern of MACF1 in both embryo and adult tissues demonstrates its important and extensive roles. To get better understanding of the physiological and pathological roles of MACF1, researchers conduct the loss-of-function studies by generating MACF1 knockout mouse models in different tissues or cells (Table 1).
MACF1 and human genetic diseases
The first instance of MACF1-related human genetic disease was reported in one family in 2014 [24]. It is a novel myopathy named as “spectraplakinopathy type I” according to that MACF1 is a member of spectraplakin family. The “spectraplakinopathy type I” is characterized by periodic hypotonia, lax muscles and diminished motor skills [24]. The genetic analysis showed that there was a duplication of the MACF1 gene on the chromosome 1p34.3, leading to overall decrease of MACF1 levels. The reduction
Conclusions and perspectives
Here we reviewed the recent findings of MACF1’s physiological and pathological roles uncovered by studies from both animal models and human diseases. Given the ubiquitously expressed pattern and multifunctional characteristics, it is not surprising that standard knockout of MACF1 results in embryonic lethality. Besides the necessity of MACF1 for embryo development, tissue-specific knockout of MACF1 reveals its critical physiological functions in skin integrity maintenance, neurodevelopment,
Acknowledgements
This work was supported by the National Natural Science Foundation of China (grant numbers 31400725, 31570940), the Project Funded by China Postdoctoral Science Foundation (grant number 2015T81051, 2017M610653), Young Talent Fund of University Association for Science and Technology in Shaanxi, China (20170401), the Fundamental Research Funds for the Central Universities (grant number 3102016ZY037), and the Shenzhen Science and Technology Project (grant number JCYJ20160229174320053).
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2019, Medical HypothesesCitation Excerpt :Thus MACF1 acts as the scaffold within the cell and supports correct assembly and function of fibers. Studies show MACF1, in general, is necessary for cytoskeleton localization and stability, protein-cytoskeleton interaction, intracellular transportation [11,12]. Focused on nervous system, MACF1 is found to be critical for neuron migration, neurite formation, synaptic function, and hippocampus-dependent learning and memory, which is also the most susceptible part in AD condition [13–16].
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2019, Molecular and Cellular EndocrinologyCitation Excerpt :Microtubule actin crosslinking factor 1 (MACF1) is a critical spectraplakin that is widely expressed in various tissues such as skin, nerve, brain and skeletal muscle (Hu et al., 2016). As a cytoskeletal linker, MACF1 has both microtubule and actin binding domains that help it regulates the dynamics of cell morphology and signal transduction during physiological and pathophysiological processes (Hu et al., 2017). It has been reported that MACF1 can regulate the migration of neurons and skin stem cells (Ka et al., 2017; Wu et al., 2011), osteoblast and neurite differentiation (Hu et al., 2018; Ka and Kim, 2016; Zhang et al., 2018), protein transport (Burgo et al., 2012), embryonic development (Chen et al., 2006), and cancer progression (Miao et al., 2017).