Cell Communication and Signaling

Overview

• ligands: chemical signals that are sent, received, and responded to by cells to communicate

Types of Cell Signaling

Autocrine Signaling

• cell releases a ligand and the ligand is sent to a receptor within the same cell

• example: cancer cells release their own growth hormones to trigger its own growth and division

Juxtacrine Signaling

• depends on direct contact between cell that is sending signal and cell that is receiving the signal

• these cells are connected by a surface receptor

• example: plasmodesmata in plants; antigen-presenting cells in human immune systems

  • plasmodesmata: small channels that directly connect the cytoplasm of neighboring plant cells to each other, establishing living bridges between cells

Paracrine Signaling

• cell secretes a ligand that travels a short distance to a nearby cell where the ligand is received

• ligands are sometimes referred to as local regulators because they only affect cells within a certain vicinity

• example: neurotransmitters, which are local regulators that travel a short distance across a synapse to communicate with nearby cells

Endocrine Signaling

• ligands travel long distances to be received by cells far away

• hormones: ligands that travel long distances

• example: insulin, which is secreted by the pancreas and travels throughout the circulatory system to trigger a response all over the body

Signal Transduction

• signal transduction: determines how a cell responds internally to a signal in the environment

  • gene expression, cell growth and division, and release of hormones depend on signal transduction

• ligands: sent out by one cell to a target cell

  • hydrophilic ligands: cannot cross phospholipid bilayer of cell membrane to enter cell; interact with receptors on cell membrane

    • binding of ligand to cell membrane receptor triggers a response inside the cell in a series of chemical reactions

  • hydrophobic ligands: can enter cell and bind to intracellular receptors in the cytosol of the cell

    • once bound to intracellular receptor, the ligand can then travel across the nuclear membrane to bind to DNA and change the expression of genes

• target cell: receives the ligand and responds depending on the ligand’s purpose

Steps of Signal Transduction

• reception: ligand binds to receptor of cell (cell membrane for hydrophilic or intracellular for hydrophobic) and causes the receptor to change shape, triggering the next step of transduction

  • receptors contain ligand-specific domains; if the ligand doesn’t match the domain it cannot bind/cell won’t respond

  • examples of receptors: g-protein coupled receptors; receptor tyrosine kinase

• transduction: a series of chemical reactions that help the cell to choose the proper response after the ligand is received; may consist of:

  • signaling cascades: series of chemical reactions in which one molecule activates others to amplify the cellular response to the signal; also called signal amplification

  • kinases: can transfer phosphate groups to other molecules to activate those molecules

  • phosphatases: can remove phosphate groups from other molecules to inactivate those molecules

  • enzymes: can produce secondary messengers

    • example: enzyme adenylyl cyclase produces secondary messenger cyclic AMP (cAMP) from ATP

• response: the result generated by the ligand; examples of cellular responses include:

  • activation of genes by steroid hormones

  • opening of ligand-gated ion channels

  • initiation of cellular processes (ex. apoptosis)

Disruptions in Signal Transduction Pathways

• receptors are specific to certain ligands; gene mutation can cause receptor to change shape and ti could no longer bind to the specific ligand

  • without functional receptor for ligand, the cell can’t respond to it and could cause disorders; examples of disorders include:

    • androgen insensitivity syndrome (AIS): when receptors for testosterone are nonfunctional in gonadal tissue (gonads cannot form during embryonic development)

    • nephrogenic diabetes insipidus (NDI): portions of structures in kidneys are insensitive to antidiuretic hormone (ADH) and urine production is affected

• molecules in environment can also interrupt signaling pathways; examples:

  • cholera toxin binds to g-protein coupled receptors, leading to interruptions that cause life-threatening dehydration

• mutations in gene for adenylyl cyclase can cause disruptions in all pathways that use secondary messenger cAMP

Feedback Mechanisms

• negative feedback: returns system to original condition and helps maintain homeostasis; examples include:

  • sweating: when body temp. becomes too high, the body will release water in the form of sweat to return the body to a lower internal temp.

  • blood glucose levels: when blood sugar gets too high, the pancreas releases insulin to lower blood glucose levels; when blood sugar gets too low, the pancreas releases glucagon, which stimulates liver cells to break down glycogen into glucose to raise blood sugar levels

• positive feedback: magnifies cellular processes/responses; examples include:

  • childbirth: hormone oxytocin stimulates uterine muscle contractions during labor; contraction of uterine muscles triggers production of more oxytocin and contractions get continuously stronger\

Cell Cycle

Phases of Cell Cycle

Interphase

• longest phase of cell cycle; consists of G1, S, and G2

• during interphase the cell grows enough so that it has enough material to divide between two daughter cells; cell also replicates genetic material (DNA) during interphase

• G1 (growth phase 1): cell grows and prepares for replication of DNA; some cellular organelles (ex. centrioles) are replicated

• S (synthesis): DNA is replicated

  • at the start: each chromosome consists of one chromatid

  • after DNA replication: each chromosome has two identical chromatids are held together by one centromere

  • at the end: cell contains twice the amount of DNA it had at the end of G1

• G2 (growth phase 2): cell continues to grow and prepare the materials needed for mitosis (ex. proteins that make up spindle fibers)

Mitosis

• goal of mitosis is to make accurate transfer of DNA from parent cell to the two daughter cells

• prophase: nuclear membrane dissolves and the chromosomes dense (becoming more visible); spindle fibers begin to form

• prometaphase: fragmentation of the nuclear envelope into many small vesicles that will eventually be divided between the future daughter cells

• metaphase: spindle fibers fully attach to centromeres of each chromosome; chromosomes are aligned at the “equator” of the cell

  • metaphase plate: center of mitotic spindle

• anaphase: each chromosome splits at its centromere into 2 as the fibers begin to shorten and pull the haves to opposite ends of the cell; each chromatid now has its own centromere and is considered a separate chromosome

  • the cell has twice the number of chromosomes as it did at the start of the cell cycle at the end of anaphase

• telophase: two new nuclear membranes form and each of the two nuclei now contain the same number of chromosomes and the same genetic information as the parent cell

Cytokinesis

• cytokinesis: division of cytoplasm (and its cellular contents) between the two daughter nuclei

• animal cells: a cleavage furrow is formed to partition the cytosol and its contents

• plant cells: they contain a cell wall; a cell plate is built within the dividing cell to provide new cell wall material for each daughter cell

Non-Dividing Cells

• cells may stop dividing temporarily or permanently if they have reached their full mature state or do not have the proper environmental conditions to divide and grow properly

• G0: non-dividing cells have exited the cell cycle and entered this phase

  • cells may enter G0 and leave the phase at any point in the cell cycle if stimulated to do so by molecular signals

Regulation of Cell Cycle, Cancer, and Apoptosis

• regulation is achieved through checkpoints during the cell cycle; if cells do not reach the conditions of the given checkpoint, they will be sent to G0

• some checkpoints are controlled by cyclins and cyclin-dependent kinases (CDKs)

  • CDKs: present at constant levels during cell cycle; can add phosphate groups to other molecules to activate them; are inactive until they bind to cyclin proteins

    • levels of cyclin proteins vary throughout cell cycle and reach their max right before mitosis

    • mitosis-promoting factor (MPF): formed when cyclins are bound to CDKs; triggers the start of mitosis

• somatic body cells: all cells not involved in sexual reproduction of organisms

  • division of somatic cells can be regulated by density-dependent inhibition

    • ex. when cells in tissues become too crowded, they stop dividing

  • anchorage dependence: exhibited by many somatic cells; cells won’t divide and grow unless they are attached to a surface

• cancer cells: are not regulated by density-dependent inhibition or anchorage dependence; can continue to grow and divide in abnormal conditions

• genes involved in cell cycle regulation:

  • proto-oncogenes: propel cell division at a specific rate; necessary for regulated and controlled cellular growth

    • oncogenes: mutated proto-ongogenes that can cause constant acceleration of cellular division and lead to formation of tumors

  • tumor suppressor genes: code for proteins that detect mutations in cells that may cause tumors to develop

    • if a single tumor suppressor gene allele mutates, the cell will still have one functional TSG allele

    • if both TSG alleles are mutated, the growth of a tumor may occur

Apoptosis

• apoptosis: programmed cell death

• may be triggered by:

  • cell acquiring a mutation that causes cancer

  • during embryonic development to ensure that various organs/structures develop (ex. hands aren’t webbed due to apoptosis)