#import "template.typ": *
#show: ams-article.with(
  title: "Reading notes: Signalling",
  authors: (
    (
      name: "<NAME>",
      department: [Department of Biology],
      organization: [Wake Forest University],
      location: [Winston Salem, NC 27101],
      email: "<EMAIL>",
      url: "www.michaeldewittjr.com"
    ),
  ),
  abstract: "Caveat Emptor",
  bibliography-file: "integratedbio.bib",
)

#set heading(numbering: "1.")
#let today = datetime.today()

= Signals and Responses

-  Receptors can be extracellular or intracellurlar
  - Extracellualr receptors activate intracelluar cascades that affect protein activity or transcription
  - Intracelluar receptors initiate transcription
- Extracelluar ligands can act locally or through long distance pathways
- Many proteins don't move into the cell but they can initiate efficient signalling
- If a protein is hydrophillic it won't move into the cell without some additional help (e.g., a channel, a chaperone protein)
- Hydrophobic and some gases can permeate the cell membrane and thus don't necessarily require chaperones or channels
- Hydrophobic molecules work through intracelluar receptors to often direct nuclear transcription
- *Steriods* are large hydrophobic molecules which are developmental signals

== Cell-cell communication

- *Contact dependent* cells touch each other
- *Paracrine*  acts through nearby cells (e.g., local mediators and signal cells interact with local targeted cells)
- *Synaptic* often in neurons which acts more locally
- *Endocrine* most common in mamalian cells where a endocrine cell enters blood stream, interacts with a receptor, then triggers target cell. 

== Response Rates

- *Gene expression* is generally slower (minutes to hours) due to the number of steps (transcription, translation, error checking)
- *Altered protein function* are fast. Typically phosphoration. 

Molecules with rapid turnover can in concentration much more dramatically.
Also describes inherit stability.
Many RNAs and proteins are unstable so they have a typically smaller halflife.
Smaller/ shorter half-lives have a more drastic impacts to signalling.

Extracellular ligands can act locally or long distance.

= Aspects of receptor function
 - Specificity 
   - Signal molecules fits binding site on its complementary receptors while other signals do not fit
   - Protein structures define the specific binding and associated affinity
   - Influenced both the hormone and receptors 
 - Amplification
   - Amplification occurs when an enzyme activate enzymes and the number of affected molecules increases geometric in an enzyme cascade
   - Amplification can within signal transduction cascades
   - For example coupled protein receptors, activates a G-protein, activates 20x cyclic AMP, binds to enzymes
  - *Kinase* adds a phosphate
 - Desensitization/ Adaption/ Feedback
   - Receptor activation triggers a feeeedback circuit that shuts off the receptor or removes it from the 
 - Integration
 - Protein complex formation
 - Concentration depdendent action