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The small EF-hand protein CALML4 functions as a critical myosin light chain within the intermicrovillar adhesion complex
- Source :
- J Biol Chem
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Specialized transporting and sensory epithelial cells employ homologous protocadherin-based adhesion complexes to remodel their apical membrane protrusions into organized functional arrays. Within the intestine, the nutrient-transporting enterocytes utilize the intermicrovillar adhesion complex (IMAC) to assemble their apical microvilli into an ordered brush border. The IMAC bears remarkable homology to the Usher complex, whose disruption results in the sensory disorder type 1 Usher syndrome (USH1). However, the entire complement of proteins that comprise both the IMAC and Usher complex are not yet fully elucidated. Using a protein isolation strategy to recover the IMAC, we have identified the small EF-hand protein calmodulin-like protein 4 (CALML4) as an IMAC component. Consistent with this finding, we show that CALML4 exhibits marked enrichment at the distal tips of enterocyte microvilli, the site of IMAC function, and is a direct binding partner of the IMAC component myosin-7b. Moreover, distal tip enrichment of CALML4 is strictly dependent upon its association with myosin-7b, with CALML4 acting as a light chain for this myosin. We further show that genetic disruption of CALML4 within enterocytes results in brush border assembly defects that mirror the loss of other IMAC components and that CALML4 can also associate with the Usher complex component myosin-7a. Our study further defines the molecular composition and protein-protein interaction network of the IMAC and Usher complex and may also shed light on the etiology of the sensory disorder USH1H.
- Subjects :
- 0301 basic medicine
Myosin Light Chains
Myosin light-chain kinase
Brush border
macromolecular substances
Biochemistry
Mice
03 medical and health sciences
Calmodulin
Chlorocebus aethiops
Myosin
otorhinolaryngologic diseases
Animals
Humans
Editors' Picks
Molecular Biology
Actin
Mice, Knockout
Myosin Type II
Myosin Heavy Chains
030102 biochemistry & molecular biology
EF hand
Chemistry
Cell Membrane
Dyneins
Cell Biology
Apical membrane
Cadherins
Brush border assembly
Cell biology
Intermicrovillar adhesion
Enterocytes
HEK293 Cells
030104 developmental biology
Myosin VIIa
COS Cells
Editors' Picks Highlights
Caco-2 Cells
Usher Syndromes
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 295
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....3f7f46bbdbd1a6b2847ca696e6877a48