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Low-Density Lipoprotein (LDL) is the primary transporter of cholesterol in the bloodstream. Cells acquire cholesterol from LDL particles through a highly specific process called  receptor-mediated endocytosis,  which is a classic example of clathrin-dependent endocytosis. This process begins when LDL particles bind to LDL receptors (LDLR) located on the  plasma membrane.  These receptors are transmembrane glycoproteins that specifically recognize apolipoprotein B-100 (ApoB-100) on the surface of LDL. The receptor-ligand complexes cluster in membrane regions called  clathrin-coated pits.  These regions are lined by the protein clathrin, which forms a polygonal lattice that shapes the invaginated membrane into a vesicle. As the clathrin-coated pit deepens, the membrane undergoes scission with the help of dynamin, a GTPase that pinches off the vesicle from the plasma membrane. This forms a clathrin-coated vesicle containing the LDL-receptor complexes. The clat...

A cell is the basic structural, functional, and biological unit of all living organisms. It is the smallest unit of life and is often referred to as the  "building block of life."  Cells carry out essential functions such as metabolism, energy production, and reproduction. Organisms can be unicellular (made of a single cell) or multicellular (composed of many cells). Discovery of the Cell Robert Hooke discovered the cell structure in 1665 by observing a thin slice of cork, specifically from the cork cambium of the cork oak tree (Quercus suber). The cork cambium is a layer of tissue found in the bark of plants that produces cork. Under his microscope, Hooke saw small, hexagon box-like compartments, which he named "cells" because they resembled the small rooms. These compartments were the cell walls of dead plant cells, a key observation that laid the foundation for the study of cell biology. Discovery of the First Living Cell The first living cell was discovered by A...

In cells, many important substances like proteins, polysaccharides, lipids and fluids are very large in size and cannot pass freely across membranes. To move these large materials safely and accurately, cells use a highly organised method called  vesicular transport.  In this process, small membrane-bound sacs known as  vesicles  are formed to carry substances either into the cell, out of the cell, or between internal compartments. Vesicular transport is an active, energy-requiring process and is carefully regulated to maintain cellular organisation. The vesicular transport mechanism occurs through a series of well-coordinated steps: Step 1: Initiation of Vesicle Formation The process begins when specific cargo molecules need to be transported. The donor membrane, often the plasma membrane or organelle membrane, starts to curve inward or outward. Special coat proteins like clathrin, COPI, or COPII are recruited to the site, which help in shaping the membrane into a b...

Endocytosis is a vital cellular process by which a cell engulfs extracellular materials by enclosing them in vesicles formed from the plasma membrane. It is an energy-dependent process (requiring ATP) that allows the internalization of nutrients, signaling molecules, fluids and even microorganisms. It helps maintain membrane composition, regulates receptor signaling and supports immune functions. This process is mainly of two types based on the presence or absence of the protein clathrin in vesicle formation. 1. Clathrin-Dependent Endocytosis Clathrin-dependent endocytosis is a highly selective and well-studied pathway where vesicles are formed with the help of a protein coat made of clathrin. The process begins when ligands (such as hormones or lipoproteins) bind to specific receptors on the cell membrane. These receptor-ligand complexes cluster together in specialized regions known as clathrin-coated pits. The clathrin lattice gives structural support and the pit invaginates, eventua...

Intermediate filaments (IFs) are one of the three main components of the cytoskeleton, along with  microtubules  and  actin filaments.  They have a very distinct and well-organized intracellular pattern which provides mechanical support, maintains cell shape and stabilizes organelle position. The pattern of their arrangement is highly regulated and follows a characteristic intracellular network that can be described as follows: 1. Perinuclear Concentration Intermediate filaments are usually concentrated around the nucleus. This region is known as the  perinuclear region.  The filaments often radiate from this area toward the cell periphery. Nuclear lamins, a type of intermediate filament, form a dense and organized meshwork just beneath the inner nuclear membrane called the  nuclear lamina.  This lamina provides structural support to the nucleus and helps in organizing chromatin. 2. Radiating Toward the Cell Periphery From the perinuclear region, ...

Vesicular traffic refers to the highly coordinated process by which proteins and lipids are transported between different compartments within the eukaryotic cell using membrane-bound vesicles. This mechanism is essential for maintaining compartmental identity, delivering newly synthesized proteins to their proper destinations, recycling membrane components and internalizing extracellular materials. The molecular mechanism of vesicular transport involves four key steps: vesicle formation, targeting, docking and fusion. 1. Vesicle Formation: The process begins at the donor membrane, where  cargo molecules  (proteins or lipids) are selected and packaged into transport vesicles. This step is mediated by coat proteins such as COPI, COPII and clathrin, which help in shaping the vesicle and selecting specific cargo. COPII-coated vesicles  transport proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. COPI-coated vesicles  are involved in retrograde transport...

Mannose-6-phosphate (M6P) residues play a critical role in the targeting and sorting of lysosomal enzymes from the trans-Golgi network to the lysosomes. This is one of the most well-known examples of protein sorting signals that help direct enzymes to their correct destination inside the cell. Lysosomes are cellular organelles responsible for breaking down macromolecules with the help of hydrolytic enzymes. These enzymes are synthesized in the rough endoplasmic reticulum (RER) and pass through the Golgi apparatus before reaching the lysosomes. However, they do not go to the lysosomes randomly. They are specifically tagged with mannose-6-phosphate residues, which act like an "address label" for lysosomal targeting. The process involves the following key steps: 1. Addition of Mannose-6-Phosphate in the Golgi: After synthesis in the RER, lysosomal enzymes enter the cis-Golgi, where they undergo post-translational modification. In the cis and medial Golgi, a special enzyme called...

One of the best-known neurotransmitters that shows both neuromodulatory and inhibitory functions is  GABA (Gamma-Aminobutyric Acid).  It is a major chemical messenger in the central nervous system (CNS) and plays a vital role in regulating brain activity. GABA is unique because it not only participates in fast synaptic transmission as an inhibitory neurotransmitter but also acts more broadly as a neuromodulator that controls the excitability of entire neural circuits. 1. GABA as a Neuromodulator As a neuromodulator, GABA works at a slower and more widespread level than fast synaptic transmission. Instead of targeting a single postsynaptic neuron, it can influence large groups of neurons or entire regions of the brain. Neuromodulatory action of GABA usually happens through GABA-B receptors, which are metabotropic and linked with second messenger systems. Through these pathways, GABA can regulate the activity of other neurotransmitter systems like: Glutamate (main excitatory neu...

The trafficking of soluble lysosomal enzymes from the trans-Golgi network (TGN) and sometimes the cell surface to the lysosomes is a highly regulated, multistep process. This mechanism ensures that lysosomal hydrolases are specifically recognized, sorted and delivered to their correct destination without getting misdirected or secreted. This sorting is based mainly on mannose-6-phosphate (M6P) tags present on the enzymes, which act as a signal for targeting. There are five major steps in this trafficking pathway: 1. Tagging with Mannose-6-Phosphate in the Golgi Apparatus Soluble lysosomal enzymes are first synthesized in the rough endoplasmic reticulum (RER) and transported to the cis-Golgi. Inside the Golgi, they are modified by a two-step enzymatic reaction: An enzyme called  N-acetylglucosamine-1-phosphotransferase  attaches a phosphorylated N-acetylglucosamine (GlcNAc-P) group to the mannose residue of the N-linked oligosaccharides on the enzyme. Another enzyme removes the...

Dopamine is a crucial neurotransmitter in the brain that plays a significant role in controlling motor functions, emotional responses and reward pathways. It is involved in regulating mood, movement and several other physiological processes. However, when there is an imbalance in dopamine secretion or its activity, it can lead to several neurological and neuropsychiatric disorders. An increase in dopamine activity is linked to certain disorders, where excessive dopamine levels in specific brain regions can lead to abnormal behaviors and symptoms. Here are two neurological disorders closely associated with increased dopamine secretion: 1. Tourette Syndrome Tourette Syndrome (TS) is a neurological disorder characterized by repetitive, involuntary movements (motor tics) and sounds (vocal tics). It often begins in childhood and can persist into adulthood. In individuals with Tourette Syndrome, there is evidence of increased dopamine activity, particularly in the  basal ganglia,  a...