Cellular extensions
Cellular extensions also known as cytoplasmic protrusions and cytoplasmic processes are those structures that project from different cells, in the body, or in other organisms. Many of the extensions are cytoplasmic protrusions such as the axon and dendrite of a neuron, known also as cytoplasmic processes.
Different glial cells project cytoplasmic processes. In the brain, the processes of astrocytes form terminal endfeet, foot processes that help to form protective barriers in the brain. In the kidneys specialised cells called podocytes extend processes that terminate in podocyte foot processes that cover capillaries in the nephron. End-processes may also be known as vascular footplates, and in general may exhibit a pyramidal or finger-like morphology. Mural cells such as pericytes extend processes to wrap around capillaries.
Foot-like processes are also present in Müller glia, pancreatic stellate cells, dendritic cells, oligodendrocytes, and others. Microglia, which are notably smaller than macroglia, can also extend their end-processes to contact areas of capillaries that are devoid of astrocyte endfeet, and thereby contribute to the formation of the glia limitans.
Other cellular extensions that protrude from the cell membrane are known as membrane protrusions or cell protrusions, also cell appendages, such as flagella, and microvilli. Microtentacles are membrane protrusions attached to free-floating malignant tumour cells, associated with the spread of some cancers.The long microtubular processes serve as attachments.
In prokaryotes such protrusions are known as surface or cell-surface appendages and include flagella, pili, fimbriae, and nanowires. Some archaea possess very complex appendages known as hami.
Types
Neuronal processes
The cytoplasmic processes of a neuron are the axons and dendrites differentiated from the precursor neuronal processes known as neurites.A dendritic spine is a membrane protrusion from a dendrite.
Glial processes
The processes of glial cells include contractile processes, and processes in astrocytes that terminate in foot processes known as endfeet.Epithelial cell processes
The podocyte is a highly specialised epithelial cell in Bowman's capsule in the kidney. Primary processes of the podocytes form terminal foot processes. The podocyte foot processes wrap around the glomerular capillaries in the kidney to function in the filtration barrier.Foot processes vs. lamellipodia and filopodia
The difference between foot processes, and lamellipodia, which are broad sheet-like protrusions, and filopodia, which are long slender pointed extensions, is that lamellipodia and filopodia are especially significant for cell movement and migration, and they are "macro" membrane protrusions. In contrast, foot processes interact with basement membranes, and are present at the "micro" scale.Image:GrowthCones.jpg|thumb|300 px|Filopodia and lamellipodia in two fluorescently-labeled growth cones.
However, cellular extensions, in general, can be found on a larger "macro" scale, occupying relatively large areas of the cell membrane. For example, microglia can use their primary processes to constantly monitor and evaluate alterations in the brain environment, and they can further deploy thin filopodia from these primary processes to expand their surveillance area.
Architectural similarities
The arborization and branching of end-processes are one of the features responsible for the structural and functional similarities among various cell types. Podocytes and pericytes share many physiological properties due to their large surface areas and intricate network of primary and secondary processes that wrap around their associated capillaries.In addition, foot processes of podocytes and dendritic extensions of neurons exhibit comparable morphological features, and molecular machinery as they both share similar proteins found at both synapses and foot processes, such as synaptopodin and dendrin. This analogy between them is further supported by their shared vulnerability to pathological conditions such as Alzheimer's disease and minimal change nephropathy, both of which are characterized by reduction and damage of dendritic spines and foot processes respectively.
Membrane protrusions
Membrane protrusions or cell appendages, extend from the cell membrane, and include microvilli, cilia, and flagella. Microvilli increase the surface area of a tissue, such as from their abundance on tissue protrusions such as intestinal villi.There is increasing evidence that membrane protrusions may act as platforms for the budding of extracellular vesicles.
Microtentacles are long microtubular processes that extend from free-floating cancer cells that serve as attachments in the spread of some cancers.
Structure
The cytoskeleton
One key distinction between cellular processes and lamellipodia lies in the composition of their cytoskeletal elements. While cellular processes can be supported by any of the three major components of the cytoskeleton—microfilaments, intermediate filaments, or microtubules—, lamellipodia are primarily driven by the polymerization of actin microfilaments, not microtubules.Microtubules are generally unable to generate the force required by lamellipodia for large-scale cell movement, as this requires a significant number of microtubules to reach the cell's leading edge in order to produce sufficient force to promote the development of significant protrusions and motility. As a result, lamellipodia are predominantly actin-based rather than microtubule-based.
On the other hand, cellular processes can be:
- Microtubule-based: Similar to neurons and dendritic cells, microtubules form the main structural core of primary processes of podocytes. In addition, oligodendrocytes possess two distinct types of microtubules:
- Radial microtubules: They are located in the proximal regions of the ramified processes of oligodendrocytes, that extend outward from the cell body.
- Lamellar microtubules: They are the microtubules that eventually wrap around the axon, forming the myelin sheath.
- Actin-based: These include terminal foot processes of podocytes and dendritic spines.
- IF-based: The predominant cytoskeletal element within astrocyte processes at birth is microtubules. However, as these cells mature, a significant shift occurs, with microtubules being almost completely replaced by intermediate filaments, composed predominantly of glial fibrillary acidic protein, found in the end-feet of Müller cells and astrocytes.
File:Gdz-0003-0019-g03.jpg|thumb|255 px| 3D Structured illumination microscopy enables visualisation of the glomerular filtration barrier, using multiplex immunofluorescence staining for markers for podocytes, endothelial cells, and the glomerular basement membrane.
File:GFAP gliosis.jpg|thumb|300 px|Confocal microscopy can reveal changes in the processes of Müller cells, in the retina, shown here in the rat. On the left, GFAP expression is predominant in the inner retinal layers. localized to the innermost layers of the retina; on the right GFAP-positive fibers show a thickening in Müller cell processes indicating gliosis.
The mitochondria
In cells with unique architecture, energy requirements can vary significantly among different cellular compartments. As a result, mitochondria, within such cells, demonstrate a non-uniform distribution, and can be strategically localized in regions with the greatest energy needs.In order to support the substantial metabolic demands of neurovascular coupling, astrocytic endfeet are loaded and packed with elongated and branched mitochondria. This represents a marked departure from the typical pattern, wherein mitochondria generally tend to become smaller as their distance from the cell body increases, particularly within the fine branches and branchlets.
However, while fine astrocytic perisynaptic processes can only house the smallest mitochondria, perivascular endfeet present a notable exception, and they can accommodate significantly more complex and ramified mitochondria. In cases of traumatic brain injury and subsequent blood-brain barrier disruption, there is even further augmentation in mitochondrial number and density within astrocytic endfeet in order to facilitate vascular remodeling as an adaptive response.
On the contrary, foot processes of podocytes are devoid of mitochondria, and mitochondria are confined to the cytosol surrounding the nucleus. The absence of mitochondria in foot processes can be attributed to the apparent size disparity, since mitochondria are generally larger than foot processes.
As a result, foot processes rely on glycolysis for their energy supply, which may be beneficial as glycolysis offers the advantage of being unrestricted by a maximum capacity. Mitochondria, on the other hand, have a maximal limit, that renders them incapable of generating additional energy upon increased demand.
Energy requirements of foot processes of podocytes
Podocytes require a significant amount of energy to preserve the structural integrity of their foot processes, given the substantial mechanical stress they endure during the glomerular filtration process.Dynamic changes in glomerular capillary pressure exert both tensile and stretching forces on podocyte foot processes, and can lead to mechanical strain on their cytoskeleton. Concurrently, fluid flow shear stress is generated by the movement of glomerular ultrafiltrate, exerting a tangential force on the surface of these foot processes.
In order to preserve their intricate foot process architecture, podocytes require a substantial ATP expenditure to maintain their structure and cytoskeletal organization, counteract the elevated glomerular capillary pressure and stabilize the capillary wall.
It has also been suggested that podocytes may possess a reasonable degree of mobility along the glomerular basement membrane, a process that may also contribute to the high energy demand. Since filtered proteins may become entrapped and accumulate under podocyte cell body and major processes, a hypothesized strategy to facilitate the removal of these stagnant proteins involves a cyclical movement of podocytes, allowing trapped proteins to be dispersed from the subpodocyte space into the filtrate.