Bulk Transport

1.         Bulk transport involves the transport of a variable number of large molecules which normally do not pass through the cell membrane by the formation of vesicles which fuses with the cell membrane to eject or inject the molecules contained within it.

2.         A vesicle is a membrane bound sac and they are transitory in nature, serving as shuttles transporting materials from the extracellular fluid to the interior of the cell and vice versa.

3.            Exocytosis:

a.         the fusion of a membrane-limited structure with the plasma membrane, resulting in the release of its contents into the extracellular space without compromising the integrity of the plasma membrane.

b.         proteins that are secreted by cells move from the endoplasmic reticulum to the Golgi apparatus, and from the trans Golgi, they are extruded into secretory granules or vesicles.

c.         the granules and vesicles move to the cell membrane.

d.         their membrane then fuses to the cell membrane, and the area of fusion breaks down.

e.         this leaves the contents of the granules or vesicles outside the cell and the cell membrane intact.

f.            because cell membranes are negatively charged, membrane structures coming close to each other will repel unless specific interactions facilitate the fusion process; hence, it is regulated by some proteins and Ca ions.

g.         There are 2 pathways by which secretion from the cell occurs: nonconstitutive and constitutive.

h.            nonconstitutive pathway:

i.          proteins initially enter secretory granules coated with clathrin.

ii.            processing of prohormones to the mature hormones occurs in these granules.

iii.         the clathrin coat is then lost and the secretory granules move to the cell membrane.

i.            constitutive pathway: involves the prompt transport of proteins to the cell membrane in vesicles that are not coated with clathrin. with little or no processing or storage.

4.            Endocytosis:

a.         the bulk intake of materials.

b.         involves the formation of an endocytotic vesicle surrounding the materials on the external membrane surface.

c.            formation of vesicles which then release the material into the cytoplasm.

d.         three types:

i.            pinocytosis.

ii.            phagocytosis.

iii.            receptor-mediated endocytosis.

5.            Pinocytosis:

a.         non specific.

b.         small invaginations of the cell membrane form and entrap extracellular fluid and anything in the fluid.

c.            pinocytotic vesicles pinch off from the cell surface and fuse with lysosomes.

d.         in the lining of endothelial cells, pinocytotic vesicles move in the opposite direction, fusing with the cell membrane and release their contents onto the cell surface.

6.            Phagocytosis:

a.         certain cell types, such as macrophages and polymorphonuclear leukocytes are specialized for incorporating and removing foreign bacteria, protozoa, fungi and damaged cells.

b.         first involves the recognition of the matter to be ingested.

c.         this then becomes enveloped by the plasma membrane which may involve the formation of cytoplasmic extensions call pseudopodia.

d.         when the particle is completely surrounded, the encompassing plasma membrane fuse and the membrane surrounding the engulfed particle forms a vesicle, known as a phagosome or endocytotic vesicle.

e.            Possible fates of endocytic vesicles:

i.            transcytosis: the vesicle can be transported to the other side of the cell and exocytose its contents intact.

ii.          fuse with other vesicles and store its contents in the cell.

iii.            undigested material may remain within membrane-bound vesicles called residual bodies, the contents of which may be later discharged at the cell surface by exocytosis or alternatively, they may accumulate in the cytoplasm.

iv.         often the endocytic vesicle (early endosome) fuse with other vesicles to form an intermediate transport vesicle (late endosome) which fuse with lysosomes.

v.         in the lysosome, hydrolytic enzymes degrade the ingested material to small molecules.

7.            Receptor-mediated Endocytosis:

a.         highly selective process which is mediated by specific receptors incorporated in the plasma membrane.

b.         ligands: molecules taken up by the receptors.

c.            receptors for many substances, such as LDL and protein hormones are located at the cell surface.

d.         the receptors are either located in small invaginations of the membrane called coated pits or drift laterally within the membrane to become localised within pits.

e.         binding of the ligand to its receptor causes widely dispersed receptors to accumulate in coated pits.

f.          coated pits are so named for a coating on the inner (cytoplasmic) aspect of the membrane by a protein called clathrin.

g.         clathrin mediates the engulfment process by formation of a curved lattice structure which governs the shape of the developing membranous structure.

f.          Uptake of Low Density Lipoproteins (LDL):

i.          LDL provide cholesterol to the tissues.

ii.            cholesterol is an essential constituent in cell membranes and is used by gland cells to make steroid hormones.

iii.         the protein constituents of the lipoproteins are called apoproteins; the major apoproteins are apo E, apo C and apo  B.

iv.         the human LDL receptor is a large, complex molecule made up of a cysteine-rich region of 292 amino acid residues that binds LDL.

v.         the receptors recognize the apo B component of LDL and binds to it.

vi.         in the process of receptor-mediated endocytosis, each coated pit is pinched off to form a coated vesicle.

vii.        the coated vesicle so formed loses their clathrin coating and are returned to the inner aspect of the plasma membrane to be reused.

viii.       the uncoated vesicle is called an endosome whose membrane contains ATP-driven H pumps that acidify their interior.

ix.         this triggers the release of LDL receptors in a separate vesicle which recycle to the cell membrane.

x.         the endosome then fuse with a lysosome containing acid lipase, which breaks down the LDL.

g.            Transferrin cycle:

i.          Fe (III) ions are carried by ferrotransferin protein.

ii.          entry into the cell by receptor-mediated endocytosis.

iii.         after endocytosis, Fe(III) is released from the transferrin-receptor complex in the early endosome (acidic CURL compartment).

iv.         the transferrin remains bound to its receptor, and they cycle to the cell surface together.

v.         when the receptor-transferrin complex encounters the neutral pH of the exterior medium, the iron-free transferrin is released.