Related Experiment Video
Updated: May 27, 2026
08:42
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
LIS1 regulates osteoclast formation and function through its interactions with dynein/dynactin and Plekhm1
Shiqiao Ye1, Tristan W Fowler, Nathan J Pavlos
1Center for Osteoporosis and Metabolic Bone Diseases, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
Plos One
|November 11, 2011
Summary
Microtubule regulator LIS1 is crucial for osteoclast function, impacting bone resorption and skeletal homeostasis. Its interaction with Plekhm1 affects microtubule organization and lysosomal secretion.
Area of Science:
- Cell Biology
- Bone Biology
- Molecular Biology
Background:
- Osteoclast activation and function are vital for bone resorption and skeletal homeostasis.
- Microtubule organization and lysosomal secretion are critical processes in osteoclast activity.
Purpose of the Study:
- To investigate the novel interaction between LIS1 and Plekhm1 in osteoclasts.
- To elucidate the role of LIS1 in osteoclast formation, function, and lysosomal secretion.
Main Methods:
- Used shRNA to decrease LIS1 expression in bone marrow macrophages.
- Assessed osteoclast formation, resorption pit formation, and CTx-I levels.
- Analyzed macrophage proliferation, osteoclast survival, differentiation, and signaling pathways (ERK, AKT, JNK).
- Investigated LIS1's interaction with dynein and its effect on microtubules.
- Examined Cathepsin K secretion and osteoclast precursor motility.
Main Results:
- LIS1 depletion significantly attenuated osteoclast formation and function.
- Reduced osteoclast formation was linked to decreased proliferation, survival, and differentiation.
- LIS1 loss disrupted microtubule organization and dynein function.
- Inhibition of Cathepsin K secretion and reduced osteoclast precursor motility were observed.
Conclusions:
- LIS1 is a novel regulator of osteoclast formation, microtubule organization, and lysosomal secretion.
- LIS1 modulates osteoclast function through its interaction with Plekhm1 and regulation of dynein.
- Findings highlight LIS1's importance in skeletal homeostasis.
Related Concept Videos
01:31Osteoclasts in Bone Remodeling
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:17Hormones and Bone Tissue
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:16Cell Motility through Blebbing
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Blebbing Through the Matrix
In multicellular...
01:32Cytoskeletal Coordination in Cell Migration
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker proteins that...