Part IV Cellular Communication

• Cellular signal transduction

• The cell cycle and programmed cell death

• Germ cells and fertilization

• Cell interactions in development

• Cancer

• Infection and immunity

Cellular SignalingCellular Signal Transduction

Gap junction

There are 3 classes of cell surface receptor

G-Protein-Coupled Receptor

cGMP

Enzyme-Linked Receptor• Second major type of cell-surface receptor• Promote growth, proliferation, differentiation, and

survival of animal cells• Growth factors and hormones are signaling

proteins• Slow response: leading to changes in gene

expression • Rapid response: effects on the cytoskeleton

(shape, and movement)• Disorders give rise to cancer• Usually has only one trans-membrane protein

Six classes of enzyme-linked receptors

1. Receptor tyrosine kinases

2. Tyrosine-kinase-associated receptors

3. Receptorlike tyrosine phosphatase

4. Receptor serine/threonine kinases

5. Receptor guanylyl cyclases

6. Histidine-kinase-associated receptors

Receptor Tyrosine Kinases

The Cell Cycle and Programmed Cell Death

• Cells are generated from cells, over three billion years ago• Cell needs to duplicate DNA and organelles and macromolecules

(in most cell) before division = growth• Several millions cells are produced every second in our body in

order to survive• If cell division is stopped (by X-ray) we will die within a few

days• Eukaryotes have evolved a complex cell-cycle control system that

control main events of the cell cycle, eg. DNA replication, segregation of chromosome, fidelity, and allow response to various signals from outside and inside cells.

• If the system is malfunction, excessive cell division can lead to cancer

Events seen under a microscope

Initiation of DNA replication

DNA replication check point

Unattached Chromosomes Block Sister-Chromatid Separation: The Spindle-Attachment Checkpoint

Controlled proteolysis by Ubiquitination (or ubiquitylation)

Ubiquitin

74 amino acid

Proteasome

APOPTOSIS

Apoptosis

• Shrinking of cell volume and nucleus• Loss of adhesion to neighboring cells• Formation of blebs at the cell surface• Fragmentation of chromatin• Rapid engulfment by phagocytosis

Apoptosis Is Mediated by an Intracellular Proteolytic Cascade

Extracellular control• Organ and body size are therefore determined by three fundamental processes:

– cell growth, – cell division– cell death. Each is independently regulated—both by intracellular programs and by extracellular signal

molecules that control these programs. • The extracellular signal molecules that regulate cell size and cell number are

– soluble secreted proteins– proteins bound to the surface of cells– components of the extracellular matrix.

• The factors that promote organ or organism growth can be operationally divided into three major classes:

– Mitogens, which stimulate cell division, primarily by relieving intracellular negative controls that otherwise block progress through the cell cycle.

– Growth factors, which stimulate cell growth (an increase in cell mass) by promoting the synthesis of proteins and other macromolecules and by inhibiting their degradation.

– Survival factors, which promote cell survival by suppressing apoptosis.

anchorage dependence of cell division