Anatomy, Histology, and Cell Biology

Histology and Cell Biology

Cell membranes consist of a lipid bilayer and associated proteins and carbohydrates. In the bilayer, the hydrophilic portions of the lipids are

arranged on the external and cytosolic surfaces, and the hydrophobic tails

are located in the interior. Transmembrane proteins are anchored to the

core of the bilayer by their hydrophobic regions and can be removed only

by detergents that disrupt the bilayer. Peripheral membrane proteins are

attached to the surface of the membrane by weak electrostatic forces and are

easy to remove by altering the pH or ionic strength of their environment

CYTOPLASM AND ORGANELLES

Cytoplasm is a dynamic fluid environment bounded by the cell membrane.

It contains various membrane-bound organelles, nonmembranous structures (such as lipid droplets, glycogen, and pigment granules), and structural or cytoskeletal proteins in either a soluble or insoluble form. The

endoplasmic reticulum (ER) is a continuous tubular meshwork that may

be either smooth (SER) or rough (RER) where studded with ribosomes.

RER is involved in protein synthesis while the SER is involved in sterioid

synthesis and detoxification. The discoid stacks (CGN, cis, medial, trans,

and TGN as one moves from the RER-side to the secretory vesicle-side) of

the Golgi apparatus are involved in packaging and routing proteins for

export or delivery to other organelles, including lysosomes and peroxisomes. Lysosomes degrade intracellular and imported debris, and peroxisomes oxidize a variety of substrates, through beta-oxidation and are the

sole source of plasmalogens. Targeting sequences include KDEL, which

targets ER proteins from the Golgi to the ER, and mannose 6-phosphate,

which targets proteins to the lysosome. Mannose 6-phosphate receptors

are found in the Golgi and in lysosomes. In the absence of mannose 6-

phosphate on lysosomal enzymes (I-cell disease) they follow the default

pathway and are secreted from the cell. Lysosomal enzymes are specific for

substrate; the absence of specific enzymes results in lysosomal storage

diseases such as Tay-Sach’s. Secretory granules leave the TGN to dock

with the plasma membrane. In that process, v-SNARE on the vesicle docks

with t-SNARE on the cell membrane and requires Rab GTPase-activity,

linking to tethering proteins, and eventually to a receptor protein in the cell

membrane. Receptor-mediated endocytosis is the process that permits

selective uptake of molecules into the cell using clathrin-coated pits and

vesicles. Molecules not recycled to the cell membrane enter early endosomes and subsequently late endosomes by way of multivesicular bodies (MVBs). The late endosome is more acidic than the early endosome

and generally leads to degradation of the molecules in lysosomes. There are

several major pathways for shuttling of receptors and ligands.

The internalized ligand-receptor complex dissociates in the early endosome with recycling of receptors [e.g., low density-lipoprotein (LDL)-

LDL-receptor complex].

• Receptor and ligand are recycled (e.g., iron-transferrin-transferrin receptorcomplex).

• The internalized ligand-recepetor complex dissociates in the late endosome and is degraded in the lysosome (e.g., growth factors such as epidermal growth factor).

• Internalized ligand-receptor passes through the cell (transcytosis) and is

released at another surface (e.g., IgA uptake by small intestinal enterocytes).

Only the nucleus, which is the repository of genetic information

stored in deoxyribonucleic acid (DNA), and the mitochondria, which are

the storage sites of energy for cellular function in the form of adenosine

triphosphate (ATP), are enclosed in double membranes. Also included in

the cytoplasm are three classes of proteins that form the cytoskeletal infrastructure: actin bundles that determine the shape of the cell; intermediate filaments that stabilize the cell membrane and cytoplasmic contents;

and microtubules (tubulin), which use molecular motors (i.e., dynein

and kinesin) to move organelles within the cell NUCLEUS

The nucleus consists of a nuclear envelope that is continuous with the ER,

chromatin, matrix, and a nucleolus the site of ribosomal ribonucleic acid

(rRNA) synthesis and initial ribosomal assembly.