Document Detail


MARCKS Actin Binding Capacity Mediates Actin Filament Assembly During Mitosis In Human Hepatic Stellate Cells.
MedLine Citation:
PMID:  22555845     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Crosslinking between the actin cytoskeleton and plasma membrane actin binding proteins is a key interaction responsible for the mechanical properties of the mitotic cell. Little is known about the identity, the localization and the function of actin filament binding proteins during mitosis in human hepatic stellate cells (hHSC). Aim of the present study was to identify and analyze the crosstalk between actin and Myristoylated Alanine-rich kinase C substrate (MARCKS), an important PKC substrate and actin filament binding protein, during mitosis in primary hHSC. Confocal analysis and chromosomal fraction analysis of mitotic hHSC demonstrated that P-MARCKS displays distinct phase-dependent localizations, accumulates at the peri-chromosomal layer and is a centrosomal protein belonging to the chromosomal cytosolic fraction. Aurora B kinase (AUBK), an important mitotic regulator, β-actin and P-MARCKS concentrate at the cytokinetic midbody during cleavage furrow formation. This localization is critical since MARCKS-depletion in hHSC is characterized by a significant loss in cytosolic actin filaments and cortical β-actin that induces cell cycle inhibition and dislocation of AUBK. A depletion of AUBK in hHSC affects cell cycle resulting in multi-nucleation. Quantitative live cell imaging demonstrates that the actin filament binding capacity of MARCKS is key to regulate mitosis since the cell cycle inhibitory effect in MARCKS-depleted cells caused abnormal cell morphology and an aberrant cytokinesis resulting in a significant increase in cell cycle time. These findings implicate that MARCKS, an important PKC substrate, is essential for proper cytokinesis and MARCKS, and its partner actin, are key mitotic regulators during cell cycle in hHSC.
Authors:
Krista Rombouts; Tommaso Mello; Francesco Liotta; Andrea Galli; Alessandra Caligiuri; Francesco Annunziato; Massimo Pinzani
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-2
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  -     ISSN:  1522-1563     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Florence.
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