For a cell to operate efficiently, the many diverse intracellular processes
        going on simultaneously must be segregated

Bacteria can survive with only a plasma membrane because they are much smaller

    - bacteria have high surface-to-volume ratios

- the bacterial PM can provide enough ATP and lipid synthesis

            - their increase in size could not have occurred without the
                    development of internal membranes
 

How does each organelle acquire its unique set of proteins?

    most organelles form from pre-existing organelles - grow and then divide

- during cell division, new proteins and lipids are incorporated
- nuclear membrane, ER, and Golgi break up into small vesicles

- distributed to both daughter cells as they form

- organelles reform

    -synthesis of almost all proteins takes place on ribosomes in cytosol
 
- a few synthesized on ribosomes in mitochondria and chloroplasts
 
some proteins are delivered directly from cytosol

    - to mitochondria, chloroplasts, peroxisomes, interior of nucleus

 
some are delivered indirectly via the ER

    - ER = the major site of lipid and protein synthesis

        -  rough ER = covered by ribosomes, processes proteins

        -  smooth ER = no ribosomes, metabolizes lipids

Secretory Pathway takes proteins from ER => Golgi => secretory vesicles
        => cell exterior

    - other proteins go from ER => Golgi => PM or chloroplast or mitochondria
            or vacuole, etc.

    - still others retained in ER or Golgi

Signal Sequence = amino acid sequences that directs proteins  to correct
                            organelle and location within the organelle

 
    - must move proteins (hydrophilic macromolecules) across the
                hydrophobic membrane barrier, often several

    - proteins without a signal sequence remain in the cytosol

    - typical signal sequences are 15-60 aa long
 

    - often but not always removed from finished protein once at target
 
               - actual signals can vary greatly, characteristics are conserved, not specific aas.
 

Proteins destined for ER, Golgi, endosomes, lysozomes, and PM
        enter ER fromcytosol while being synthesized

- targeted by signal sequence

- entry begins before polypeptide synthesis is complete

Water soluble proteins are translocated completely across ER membrane and
        released in lumen

  - destined for secretion from the cell or lumen of another organelle

        - destined to remain there or move to the membrane of another organelle or PM

        - N-terminal signal initiates translocation, internal signal terminates

        - 2nd sequence moves sideways into membrane and becomes embedded

                -  anchored by membrane-spanning alpha-helices

        - repeated for proteins w/ multiple membrane-spanning regions

                - multiple pairs of start- and stop-transfer sequences
 

Polypeptide chains are folded into their correct 3-D conformations in the ER

        -  carried out by chaperones (e.g. BiP, a Hsp70), protein disulfide isomerase

                - correctly-folded proteins released by BiP, sent to Golgi

                -  abnormally-folded proteins remain bound to BiP, retained in ER or degraded

        -  The ER is also the site of N-linked glycosylation and addition of GPI anchors
 

Proteins and lipids are transported in vesicles from the ER to the Golgi

    -  resident ER proteins are marked by c-terminal sequences (KDEL and KKXX)
            that signal their return from the Golgi to the ER by a recycling program

    -  other targeting sequences mediate the selective packaging of exported proteins 
            into vesicles that transport them to the Golgi
 

The Golgi functions in protein processing and sorting, and lipid and polysaccharide synthesis

    -  proteins arrive from the ER at the cis Golgi

    -  from there, they are transported to the Golgi stack = site of metabolic activities

            - N-linked oligosaccharides are modified in Golgi

            - O-linked glycosylation takes place in Golgi

            - glycolipids, sphingomyelin, and plant cell wall polysaccharides are made in Golgi

    -  modified proteins sorted and packaged into vesicles in the trans Golgi

    -  vesicles transported to PM, lysosomes, vacuoles, or secreted from cell.

        Transport vesicles - continually budding and fusing to mediate transfer

- outward from ER to PM = secretory pathway

- side branch to endosomes and lysosomes

- inward from PM to lysozomes = endocytic pathway

- ingestion and degradation of extracellular molecules

- route of communication between interior of cell and its surroundings

Vesicle budding is driven by assembly of a protein coat = Coated Vesicles

- several types of protein coats - clathrin and COP are best known

- aid in formation of bud and in binding molecules for transport

- recognize which vesicles go where

- coat is lost after budding is completed, allows membrane to fuse

The specificity of vesicle docking depends on SNAREs

- binding of complementary SNARE proteins leads to  vesicle docking

                    - Rab proteins = family of small GTP-binding proteins that interact
                                                at multiple steps of the vesicle transport process

                    - membrane fusion requires additional proteins and energy
 
 

Lysosomes degrade proteins, nucleic acids, polysaccharides, and lipids

        - contain array of acid hydrolases that function in acidic pH inside lysosomes

    Endocytosis = process by which extracellular molecules are taken up and transported
                            to endosomes, which mature into lysosomes as acid hydrolases
                            are delivered from Golgi

    Phagocytosis = process by which large particles are taken up into cell

            - e.g. bacteria, cell debris

            - usually specialized cells like macrophages

            - phagosomes = phagocytic vacuoles that fuse w/lysosomes

    Autophagy = gradual digestion of the cell's own components

           - cytoplasmic proteins and organelles are enclosed in vesicles from ER

           - those vesicles fuse with lysosomes