scholarly journals Kinesin motors and primary cilia

2011 ◽  
Vol 39 (5) ◽  
pp. 1120-1125 ◽  
Author(s):  
Kristen J. Verhey ◽  
John Dishinger ◽  
Hooi Lynn Kee
Keyword(s):  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Intraflagellar Transport ◽  
Cell Types ◽  
Cellular Motility ◽  
Form And Function ◽  
Cilia And Flagella ◽  
Protein Components ◽  
And Function ◽  
Kidney Liver

Cilia and flagella play important roles in human health by contributing to cellular motility as well as sensing and responding to environmental cues. Defects in ciliary assembly and/or function can lead to a range of human diseases, collectively known as the ciliopathies, including polycystic kidney, liver and pancreatic diseases, sterility, obesity, situs inversus, hydrocephalus and retinal degeneration. A basic understanding of how cilia form and function is essential for deciphering ciliopathies and generating therapeutic treatments. The cilium is a unique compartment that contains a distinct complement of protein and lipid. However, the molecular mechanisms by which soluble and membrane protein components are targeted to and trafficked into the cilium are not well understood. Cilia are generated and maintained by IFT (intraflagellar transport) in which IFT cargoes are transported along axonemal microtubules by kinesin and dynein motors. A variety of genetic, biochemical and cell biological approaches has established the heterotrimeric kinesin-2 motor as the ‘core’ IFT motor, whereas other members of the kinesin-2, kinesin-3 and kinesin-4 families function as ‘accessory’ motors for the transport of specific cargoes in diverse cell types. Motors of the kinesin-9 and kinesin-13 families play a non-IFT role in regulating ciliary beating or axonemal length, respectively. Entry of kinesin motors and their cargoes into the ciliary compartment requires components of the nuclear import machinery, specifically importin-β2 (transportin-1) and Ran-GTP (Ran bound to GTP), suggesting that similar mechanisms may regulate entry into the nuclear and ciliary compartments.

scholarly journals A key regulatory protein for flagellum length control in stable flagella

2019 ◽  
Author(s):  
Madison Atkins ◽  
Jiří Týč ◽  
Shahaan Shafiq ◽  
Manu Ahmed ◽  
Eloïse Bertiaux ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Regulatory Protein ◽  
Length Change ◽  
Cell Types ◽  
Basal Bodies ◽  
Locking Mechanism ◽  
Cilia And Flagella ◽  
Eukaryotic Organisms

SummaryCilia and flagella are highly conserved microtubule-based organelles that have important roles in cell motility and sensing [1]. They can be highly dynamic and short lived such as primary cilia or Chlamydomonas [2] or very stable and long lived such as those in spermatozoa [3] photoreceptors [4] or the flagella of many protist cells [3,4]. Although there is a wide variation in length between cell types, there is generally a defined length for a given cell type [1]. Many unicellular flagellated and ciliated organisms have an additional challenge as they must maintain flagella/cilia at a defined length whilst also growing new flagella/cilia in the same cell. It is not currently understood how this is achieved. A grow-and-lock model was proposed for the maintenance of stable flagella where a molecular lock is applied to prevent flagellum length change after assembly [5]. The molecular mechanisms of how this lock operates are unknown, but could be important in cells where an existing flagellum must be maintained whilst a new flagellum assembles. Here we show that Cep164C contributes to the locking mechanism at the base of the flagellum in Trypanosoma brucei. It is only localised on the transition fibres of basal bodies of fully assembled flagella and missing from assembling flagella. In fact, basal bodies only acquire Cep164C in the third cell cycle after they assemble in trypanosomes. Depletion leads to dysregulation of flagellum growth with both longer and shorter flagella; consistent with defects in a flagellum locking mechanism. By controlling delivery of components into the old assembled flagellum, maintenance of stable flagella can occur but limits further growth. This offers an important explanation for how many eukaryotic unicellular cells maintain their existing flagella whilst growing new ones before these cells divide. This work also reveals additional regulatory roles for Cep164 in eukaryotic organisms.

scholarly journals Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Ugochukwu Kelvin Ihenacho ◽  
Kelsey A. Meacham ◽  
Megan Cleland Harwig ◽  
Michael E. Widlansky ◽  
R. Blake Hill
Keyword(s):  
Human Health ◽  
Neurological Disorders ◽  
Mitochondrial Fission ◽  
Cell Types ◽  
Mitochondrial Division ◽  
Form And Function ◽  
Health And Disease ◽  
Genetic Deletion ◽  
And Function

Mitochondrial fission protein 1 (Fis1) was identified in yeast as being essential for mitochondrial division or fission and subsequently determined to mediate human mitochondrial and peroxisomal fission. Yet, its exact functions in humans, especially in regard to mitochondrial fission, remains an enigma as genetic deletion of Fis1 elongates mitochondria in some cell types, but not others. Fis1 has also been identified as an important component of apoptotic and mitophagic pathways suggesting the protein may have multiple, essential roles. This review presents current perspectives on the emerging functions of Fis1 and their implications in human health and diseases, with an emphasis on Fis1’s role in both endocrine and neurological disorders.

Form and Function in Cells of the Brain

The Neuron ◽  
2015 ◽  
pp. 23-38
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Critical Role ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Cell Body ◽  
Long Distance ◽  
Form And Function ◽  
And Function ◽  
The Brain

This chapter examines unique mechanisms that the neuron has evolved to establish and maintain the form required for its specialized signaling functions. Unlike some other organs, the brain contains a variety of cell types including several classes of glial cells, which play a critical role in the formation of the myelin sheath around axons and may be involved in immune responses, synaptic transmission, and long-distance calcium signaling in the brain. Neurons share many features in common with other cells (including glia), but they are distinguished by their highly asymmetrical shapes. The neuronal cytoskeleton is essential for establishing this cell shape during development and for maintaining it in adulthood. The process of axonal transport moves vesicles and other organelles to regions remote from the neuronal cell body. Proteins such as kinesin and dynein, called molecular motors, make use of the energy released by hydrolysis of ATP to drive axonal transport.

scholarly journals Multi-species comparisons of snakes identify coordinated signalling networks underlying post-feeding intestinal regeneration

2019 ◽  
Vol 286 (1906) ◽  
pp. 20190910 ◽  
Author(s):  
Blair W. Perry ◽  
Audra L. Andrew ◽  
Abu Hena Mostafa Kamal ◽  
Daren C. Card ◽  
Drew R. Schield ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Growth Stress ◽  
Comparative Approach ◽  
Snake Species ◽  
Form And Function ◽  
Post Feeding ◽  
Intestinal Regeneration ◽  
Regenerative Growth ◽  
Hypothesis Model ◽  
And Function

Several snake species that feed infrequently in nature have evolved the ability to massively upregulate intestinal form and function with each meal. While fasting, these snakes downregulate intestinal form and function, and upon feeding restore intestinal structure and function through major increases in cell growth and proliferation, metabolism and upregulation of digestive function. Previous studies have identified changes in gene expression that underlie this regenerative growth of the python intestine, but the unique features that differentiate this extreme regenerative growth from non-regenerative post-feeding responses exhibited by snakes that feed more frequently remain unclear. Here, we leveraged variation in regenerative capacity across three snake species—two distantly related lineages ( Crotalus and Python ) that experience regenerative growth, and one ( Nerodia ) that does not—to infer molecular mechanisms underlying intestinal regeneration using transcriptomic and proteomic approaches. Using a comparative approach, we identify a suite of growth, stress response and DNA damage response signalling pathways with inferred activity specifically in regenerating species, and propose a hypothesis model of interactivity between these pathways that may drive regenerative intestinal growth in snakes.

scholarly journals Epigenetic Regulation of the Hippocampus, with Special Reference to Radiation Exposure

2020 ◽  
Vol 21 (24) ◽  
pp. 9514
Author(s):  
Genevieve Saw ◽  
Feng Ru Tang
Keyword(s):  
Epigenetic Regulation ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Epigenetic Changes ◽  
Epigenetic Factors ◽  
Hippocampal Function ◽  
Neuropsychological Disorders ◽  
Radiation Induced ◽  
Non Coding Rnas ◽  
And Function

The hippocampus is crucial in learning, memory and emotion processing, and is involved in the development of different neurological and neuropsychological disorders. Several epigenetic factors, including DNA methylation, histone modifications and non-coding RNAs, have been shown to regulate the development and function of the hippocampus, and the alteration of epigenetic regulation may play important roles in the development of neurocognitive and neurodegenerative diseases. This review summarizes the epigenetic modifications of various cell types and processes within the hippocampus and their resulting effects on cognition, memory and overall hippocampal function. In addition, the effects of exposure to radiation that may induce a myriad of epigenetic changes in the hippocampus are reviewed. By assessing and evaluating the current literature, we hope to prompt a more thorough understanding of the molecular mechanisms that underlie radiation-induced epigenetic changes, an area which can be further explored.

scholarly journals Examining Form and Function of Dendritic Spines

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kevin F. H. Lee ◽  
Cary Soares ◽  
Jean-Claude Béïque
Keyword(s):  
Dendritic Spines ◽  
Laser Scanning ◽  
Molecular Mechanisms ◽  
Laser Scanning Microscopy ◽  
Spine Morphology ◽  
Functional Changes ◽  
Form And Function ◽  
Spine Structure ◽  
And Function ◽  
The Relationship

The majority of fast excitatory synaptic transmission in the central nervous system takes place at protrusions along dendrites called spines. Dendritic spines are highly heterogeneous, both morphologically and functionally. Not surprisingly, there has been much speculation and debate on the relationship between spine structure and function. The advent of multi-photon laser-scanning microscopy has greatly improved our ability to investigate the dynamic interplay between spine form and function. Regulated structural changes occur at spines undergoing plasticity, offering a mechanism to account for the well-described correlation between spine size and synapse strength. In turn, spine structure can influence the degree of biochemical and perhaps electrical compartmentalization at individual synapses. Here, we review the relationship between dendritic spine morphology, features of spine compartmentalization and synaptic plasticity. We highlight emerging molecular mechanisms that link structural and functional changes in spines during plasticity, and also consider circumstances that underscore some divergence from a tight structure-function coupling. Because of the intricate influence of spine structure on biochemical and electrical signalling, activity-dependent changes in spine morphology alone may thus contribute to the metaplastic potential of synapses. This possibility asserts a role for structural dynamics in neuronal information storage and aligns well with current computational models.

scholarly journals A comprehensive guide to the ROMK potassium channel: form and function in health and disease

2009 ◽  
Vol 297 (4) ◽  
pp. F849-F863 ◽  
Author(s):  
Paul A. Welling ◽  
Kevin Ho
Keyword(s):  
Potassium Channel ◽  
Molecular Mechanisms ◽  
Atomic Level ◽  
Structural Basis ◽  
Potassium Homeostasis ◽  
Form And Function ◽  
Founding Member ◽  
Channel Form ◽  
Health And Disease ◽  
And Function

The discovery of the renal outer medullary K+channel (ROMK, Kir1.1), the founding member of the inward-rectifying K+channel (Kir) family, by Ho and Hebert in 1993 revolutionized our understanding of potassium channel biology and renal potassium handling. Because of the central role that ROMK plays in the regulation of salt and potassium homeostasis, considerable efforts have been invested in understanding the underlying molecular mechanisms. Here we provide a comprehensive guide to ROMK, spanning from the physiology in the kidney to the organization and regulation by intracellular factors to the structural basis of its function at the atomic level.

scholarly journals Characterization of primary cilia features reveal cell-type specific variability in in vitro models of osteogenic and chondrogenic differentiation

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9799
Author(s):  
Priyanka Upadhyai ◽  
Vishal Singh Guleria ◽  
Prajna Udupa
Keyword(s):  
Cell Lines ◽  
Chondrogenic Differentiation ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Types ◽  
Treatment Modalities ◽  
Cell Type ◽  
Cell Type Specific

Primary cilia are non-motile sensory antennae present on most vertebrate cell surfaces. They serve to transduce and integrate diverse external stimuli into functional cellular responses vital for development, differentiation and homeostasis. Ciliary characteristics, such as length, structure and frequency are often tailored to distinct differentiated cell states. Primary cilia are present on a variety of skeletal cell-types and facilitate the assimilation of sensory cues to direct skeletal development and repair. However, there is limited knowledge of ciliary variation in response to the activation of distinct differentiation cascades in different skeletal cell-types. C3H10T1/2, MC3T3-E1 and ATDC5 cells are mesenchymal stem cells, preosteoblast and prechondrocyte cell-lines, respectively. They are commonly employed in numerous in vitro studies, investigating the molecular mechanisms underlying osteoblast and chondrocyte differentiation, skeletal disease and repair. Here we sought to evaluate the primary cilia length and frequencies during osteogenic differentiation in C3H10T1/2 and MC3T3-E1 and chondrogenic differentiation in ATDC5 cells, over a period of 21 days. Our data inform on the presence of stable cilia to orchestrate signaling and dynamic alterations in their features during extended periods of differentiation. Taken together with existing literature these findings reflect the occurrence of not only lineage but cell-type specific variation in ciliary attributes during differentiation. These results extend our current knowledge, shining light on the variabilities in primary cilia features correlated with distinct differentiated cell phenotypes. It may have broader implications in studies using these cell-lines to explore cilia dependent cellular processes and treatment modalities for skeletal disorders centered on cilia modulation.

scholarly journals To form and function: on the role of basement membrane mechanics in tissue development, homeostasis and disease

Open Biology ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 200360
Author(s):  
Nargess Khalilgharibi ◽  
Yanlan Mao
Keyword(s):  
Basement Membrane ◽  
Molecular Mechanisms ◽  
Disease Diagnosis ◽  
Membrane Mechanics ◽  
Form And Function ◽  
And Function ◽  
Tissue Form

The basement membrane (BM) is a special type of extracellular matrix that lines the basal side of epithelial and endothelial tissues. Functionally, the BM is important for providing physical and biochemical cues to the overlying cells, sculpting the tissue into its correct size and shape. In this review, we focus on recent studies that have unveiled the complex mechanical properties of the BM. We discuss how these properties can change during development, homeostasis and disease via different molecular mechanisms, and the subsequent impact on tissue form and function in a variety of organisms. We also explore how better characterization of BM mechanics can contribute to disease diagnosis and treatment, as well as development of better in silico and in vitro models that not only impact the fields of tissue engineering and regenerative medicine, but can also reduce the use of animals in research.

scholarly journals Subcellular Specialization of Mitochondrial Form and Function in Skeletal Muscle Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
T. Bradley Willingham ◽  
Peter T. Ajayi ◽  
Brian Glancy
Keyword(s):  
Skeletal Muscle ◽  
Energy Homeostasis ◽  
Single Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Current Data ◽  
Skeletal Muscle Cells ◽  
Form And Function ◽  
Mitochondrial Heterogeneity ◽  
And Function

Across different cell types and within single cells, mitochondria are heterogeneous in form and function. In skeletal muscle cells, morphologically and functionally distinct subpopulations of mitochondria have been identified, but the mechanisms by which the subcellular specialization of mitochondria contributes to energy homeostasis in working muscles remains unclear. Here, we discuss the current data regarding mitochondrial heterogeneity in skeletal muscle cells and highlight potential new lines of inquiry that have emerged due to advancements in cellular imaging technologies.

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